AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA)

• ClinicalTrials.gov Identifier: NCT02296125
• Recruitment Status: Active, not recruiting
• First Posted: November 20, 2014
• Results First Posted: November 6, 2018
• Last Update Posted: March 27, 2023
• Sponsor: AstraZeneca
• Collaborator: Parexel
• Information provided by (Responsible Party): AstraZeneca

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer
• Interventions: Drug: AZD9291 80 mg/40 mg + placebo; Drug: Placebo Erlotinib 150/100mg; Drug: Placebo Gefitinib 250 mg; Drug: Erlotinib 150/100 mg; Drug: Gefitinib 250 mg; Drug: Placebo AZD9291 80 mg/ 40 mg
• Enrollment: 674

Participant Flow

Recruitment Details	A total of 556 participants in Global cohort (out of 673 participants in Global and China cohorts) were randomized to treatment at 132 study centres in 29 countries. An additional 117 participants in 19 centres were enrolled into the China extension cohort only.
Pre-assignment Details	During the 28 day screening period, participants were enrolled based on the presence in their tumour of at least 1 of the 2 most frequent Epidermal growth factor receptor (EGFR) mutations. At the time of enrolment, all participants were required to provide biopsy tissue for central testing of the Exon 19 deletion (Ex19del) and L858R mutations

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Period Title: Overall Study
Started [1]	279	277 [2]	71 [3]	65 [4]
Completed [5]	61	13	15	3
Not Completed	218	264	56	62
Reason Not Completed
Withdrawal by Subject	18	8	6	2
Adverse Event	41	52	9	4
Severe non-compliance to protocol	0	1	0	0
Condition under investigation worsened	153	199	39	56
Any reason not specifically recorded	6	4	2	0
[1] There were 19 participants double counted which shows the total participants of 692.; [2] 183 participant received gefitinib and 93 participants received erlotinib.; [3] There were 12 participants who were in both the Global and China Extension Osimertinib Arm.; [4] There were 7 participants who were in both the Global and China Extension SoC EGFR-TKI Arm.; [5] Participants ongoing study treatment at data cut-off

Baseline Characteristics

Arm/Group Title		Global + China Extension Osimertinib Arm	Global + China Extension SoC EGFR-TKI Arm	Total
Arm/Group Description		All participants who were enrolled in Osimertinib Arm for either the global or China Extension study.	All participants who were enrolled in SoC EGFR-TKI Arm for either the Global or China Extension study	Total of all reporting groups
Overall Number of Baseline Participants		338	335	673
Baseline Analysis Population Description		There were 12 participants who were in both the Global and China Extension Osimertinib Arm and 7 participants in both the Global and China Extension SoC EGFR-TKI arm.
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
Global cohort	Number Analyzed	279 participants	277 participants	556 participants
		62.7 (10.70)	63.3 (10.90)	63.0 (10.79)
China Cohort	Number Analyzed	71 participants	65 participants	136 participants
		59.1 (9.66)	59.0 (10.94)	59.0 (10.26)
		[1] Measure Analysis Population Description: Each study is reported in a seprate row. There were 12 participants who were in both the Global and China Extension Osimertinib Arm, and 7 particicpants in both the Global and China Extension SoC EGFR-TKI arm.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global cohort	Number Analyzed	279 participants	277 participants	556 participants
	Female	178 63.8%	172 62.1%	350 62.9%
	Male	101 36.2%	105 37.9%	206 37.1%
China Cohort	Number Analyzed	71 participants	65 participants	136 participants
	Female	43 60.6%	46 70.8%	89 65.4%
	Male	28 39.4%	19 29.2%	47 34.6%
		[1] Measure Analysis Population Description: Each study is reported in a seprate row. There were 12 participants who were in both the Global and China Extension Osimertinib Arm, and 7 particicpants in both the Global and China Extension SoC EGFR-TKI arm.
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
	American Indian or Alaska Native	1 0.4%	1 0.4%	2 0.4%
	Asian	174 62.4%	173 62.5%	347 62.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 0.7%	2 0.7%	4 0.7%
	White	101 36.2%	100 36.1%	201 36.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 0.4%	1 0.4%	2 0.4%
China Cohort	Number Analyzed	71 participants	65 participants	136 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	71 100.0%	65 100.0%	136 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: Each study is reported in a seprate row. There were 12 participants who were in both the Global and China Extension Osimertinib Arm, and 7 particicpants in both the Global and China Extension SoC EGFR-TKI arm.
Race/Ethnicity, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Asian-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		77 27.6%	94 33.9%	171 30.8%
Chinese-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		32 11.5%	24 8.7%	56 10.1%
Japanese-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		65 23.3%	55 19.9%	120 21.6%
Other-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		103 36.9%	104 37.5%	207 37.2%
Missing-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		2 0.7%	0 0.0%	2 0.4%
Hispanic or Latino-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		0 0.0%	0 0.0%	0 0.0%
Chinese-China cohort	Number Analyzed	71 participants	65 participants	136 participants
		71 100.0%	65 100.0%	136 100.0%
		[1] Measure Analysis Population Description: Each study is reported in a seprate row. There were 12 participants who were in both the Global and China Extension Osimertinib Arm, and 7 particicpants in both the Global and China Extension SoC EGFR-TKI arm.
Smoking status [1]; Measure Type: Count of Participants; Unit of measure: Participants
Never smoked-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		182 65.2%	175 63.2%	357 64.2%
Current smokers-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		8 2.9%	9 3.2%	17 3.1%
Former smokers-Global Cohort	Number Analyzed	279 participants	277 participants	556 participants
		89 31.9%	93 33.6%	182 32.7%
Never smoked-China Cohort	Number Analyzed	71 participants	65 participants	136 participants
		53 74.6%	50 76.9%	103 75.7%
Current smokers-China Cohort	Number Analyzed	71 participants	65 participants	136 participants
		3 4.2%	4 6.2%	7 5.1%
Former smokers-China Cohort	Number Analyzed	71 participants	65 participants	136 participants
		15 21.1%	11 16.9%	26 19.1%
		[1] Measure Analysis Population Description: Each study is reported in a seprate row. There were 12 participants who were in both the Global and China Extension Osimertinib Arm, and 7 particicpants in both the Global and China Extension SoC EGFR-TKI arm.

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival (PFS) (Months)
Description	Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. The primary endpoint of PFS was based on Investigator assessment.
Time Frame	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed	279	277	71	65
Median (95% Confidence Interval); Unit of Measure: Months
	18.9; (15.2 to 21.4)	10.2; (9.6 to 11.1)	17.8; (13.6 to 20.7)	9.8; (8.3 to 13.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (Global Cohort), SoC EGFR-TKI (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.57
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (China Cohort), SoC EGFR-TKI (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The china cohort was not powered for superiority
Statistical Test of Hypothesis	P-Value	0.0065
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.85
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months
Description	Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS.
Time Frame	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed	279	277	71	65
Measure Type: Number; Unit of Measure: Percentage of Participants
Progression free at 6 months (%)	88.4	75.2	78.8	72.3
Progression free at 12 months (%)	68.2	42.3	67.3	44.6
Progression free at 18 months (%)	50.9	24.4	46.9	25.8

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR was defined as the number (%) of participants with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. ORR was based on Investigator assessment.
Time Frame	At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed	279	277	71	65
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	76.7; (71.29 to 81.53)	69.0; (63.14 to 74.35)	76.1; (64.5 to 85.4)	70.8; (58.2 to 81.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (Global Cohort), SoC EGFR-TKI (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.036
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; 1.03 to 2.22
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (China Cohort), SoC EGFR-TKI (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The china cohort was not powered for superiority
Statistical Test of Hypothesis	P-Value	0.485
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.61 to 2.84
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Duration of Response (DoR)
Description	Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.
Time Frame	At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed	279	277	71	65
Median (95% Confidence Interval); Unit of Measure: Months
	17.2; (13.8 to 22.0)	8.5; (7.3 to 9.8)	16.4 [1]; (12.3 to NA)	10.9; (8.3 to 13.8)

[1]

NA-Upper limit is not calculable at this data cut-off.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (China Cohort), SoC EGFR-TKI (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The china cohort was not powered for superiority
Statistical Test of Hypothesis	P-Value	0.0133
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.48
	Confidence Interval	(2-Sided) 95%; 1.21 to 5.09
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (Global Cohort), SoC EGFR-TKI (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.27
	Confidence Interval	(2-Sided) 95%; 1.68 to 3.08
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	The DCR was defined as the percentage of participants who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.
Time Frame	At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed	279	277	71	65
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	97.1; (94.4 to 98.8)	92.4; (88.6 to 95.2)	97.2; (90.2 to 99.7)	95.4; (87.1 to 99.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (Global Cohort), SoC EGFR-TKI (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0110
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.78
	Confidence Interval	(2-Sided) 95%; 1.25 to 6.78
	Estimation Comments	An odds ratio > 1 favours osimertinib

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (China Cohort), SoC EGFR-TKI (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The china cohort was not powered for superiority
Statistical Test of Hypothesis	P-Value	0.5772
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.67
	Confidence Interval	(2-Sided) 95%; 0.27 to 12.98
	Estimation Comments	An odds ratio >1 favours osimertinib

6. Secondary Outcome

Title	Depth of Response
Description	The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
Time Frame	At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed	279	277	71	65
Mean (Standard Deviation); Unit of Measure: percentage of change
	-52.36 (25.065)	-45.66 (28.270)	-49.17 (24.303)	-42.92 (26.814)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (Global Cohort), SoC EGFR-TKI (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0025
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.80
	Confidence Interval	(2-Sided) 95%; -11.205 to -2.403
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (China Cohort), SoC EGFR-TKI (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The china cohort was not powered for superiority
Statistical Test of Hypothesis	P-Value	0.1348
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.59
	Confidence Interval	(2-Sided) 95%; -15.246 to 2.072
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Overall Survival (OS)- Number of Participants With an Event
Description	Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
Time Frame	From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months)

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed	279	277	71	65
Measure Type: Count of Participants; Unit of Measure: Participants
Death	155 55.6%	166 59.9%	45 63.4%	44 67.7%
Still in survival follow-up	104 37.3%	86 31.0%	25 35.2%	17 26.2%
Terminated prior to death	20 7.2%	25 9.0%	1 1.4%	4 6.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (Global Cohort), SoC EGFR-TKI (Global Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0462
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.799
	Confidence Interval	(2-Sided) 95%; 0.6409 to 0.9963
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Osimertinib 80 mg (China Cohort), SoC EGFR-TKI (China Cohort)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The china cohort was not powered for superiority
Statistical Test of Hypothesis	P-Value	0.4416
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.848
	Confidence Interval	(2-Sided) 95%; 0.5568 to 1.2910
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Plasma Concentrations of AZD9291
Description	To characterise the pharmacokinetics (PK) of osimertinib
Time Frame	Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis set (osimertinib arm only) was defined as participants in the FAS who had at least 1 evaluable PK concentration and who had no detectable pre-dose osimertinib concentrations above the lower limit of quantitation (LLQ) on Cycle 1 Day 1.

Arm/Group Title		Osimertinib 80 mg (Global Cohort)	Osimertinib 80 mg (China Cohort)
Arm/Group Description:		Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participants received Osimertinib 80 mg orally once daily (QD)
Overall Number of Participants Analyzed		279	71
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Nano moles
Cycle 1 Day 1-Predose	Number Analyzed	199 participants	69 participants
		NA [1]; (NA%)	NA [1]; (NA%)
Cycle 1 Day 1-0.5 - 2 hours	Number Analyzed	203 participants	69 participants
		4.9487; (1173.3679%)	5.0249; (816.7305%)
Cycle 1 Day 1-3 - 5 hours	Number Analyzed	211 participants	69 participants
		129.3340; (171.2983%)	131.5669; (120.5979%)
Cycle 3 Day 1- Predose	Number Analyzed	183 participants	67 participants
		394.3489; (43.9296%)	441.5606; (55.0039%)
Cycle 3 Day 1, 0.5 - 2 hours	Number Analyzed	183 participants	68 participants
		397.7406; (45.8548%)	441.7343; (60.0626%)
Cycle 3 Day 1, 3 - 5 hours	Number Analyzed	182 participants	67 participants
		512.4012; (44.0653%)	553.8090; (60.9883%)
Cycle 5 Day 1, Predose	Number Analyzed	180 participants	67 participants
		358.5487; (53.8212%)	419.5893; (63.2507%)
Cycle 5 Day 1, 0.5 - 2 hours	Number Analyzed	177 participants	67 participants
		369.0696; (51.3284%)	426.8197; (60.3841%)
Cycle 5 Day 1, 3-5 hours	Number Analyzed	179 participants	67 participants
		485.8142; (47.2759%)	570.7729; (61.4401%)
Cycle 7 Day 1-Predose	Number Analyzed	181 participants	62 participants
		347.6176; (47.7442%)	397.5857; (54.9006%)
Cycle 7 Day 1-0.5 - 2 hours	Number Analyzed	179 participants	61 participants
		357.8529; (45.0713%)	411.6170; (49.4107%)
Cycle 7 Day 1-3-5 hours	Number Analyzed	179 participants	62 participants
		475.6587; (41.5778%)	530.7212; (56.5184%)
Cycle 9 Day 1-Predose	Number Analyzed	165 participants	62 participants
		359.5284; (47.0592%)	383.2238; (67.7153%)
Cycle 9 Day 1-0.5-2 hours	Number Analyzed	165 participants	61 participants
		363.0106; (48.3837%)	395.2179; (71.5532%)
Cycle 9 Day 1-3-5 hours	Number Analyzed	163 participants	62 participants
		485.6006; (46.6459%)	490.5964; (70.3383%)
Cycle 11 Day 1-Predose	Number Analyzed	158 participants	59 participants
		354.5330; (44.4308%)	410.4023; (66.2329%)
Cycle 11 Day 1-0.5 -2 hours	Number Analyzed	160 participants	59 participants
		367.7450; (45.2003%)	415.2427; (64.6174%)
Cycle 11 Day 1-3-5 hours	Number Analyzed	161 participants	59 participants
		476.4472; (44.4457%)	528.8081; (68.4645%)
Cycle 13 Day 1-Predose	Number Analyzed	150 participants	55 participants
		369.9834; (40.1071%)	404.2678; (62.0291%)
Cycle 13 Day 1-0.5 -2 hours	Number Analyzed	147 participants	54 participants
		371.4157; (42.9794%)	393.1688; (62.1053%)
Cycle 13 Day 1-3-5 hours	Number Analyzed	147 participants	55 participants
		496.6866; (40.8757%)	499.0220; (62.5485%)

[1]

NA as values were not calculable and non-quantifiable

9. Secondary Outcome

Title	Plasma Concentrations of Metabolites AZ5104
Description	To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ5104.
Time Frame	Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis set (osimertinib arm only) was defined as participants in the FAS who had at least 1 evaluable PK concentration and who had no detectable pre-dose osimertinib concentrations above the lower limit of quantitation (LLQ) on Cycle 1 Day 1.

Arm/Group Title		Osimertinib 80 mg (Global Cohort)	Osimertinib 80 mg (China Cohort)
Arm/Group Description:		Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participants received Osimertinib 80 mg orally once daily (QD)
Overall Number of Participants Analyzed		279	71
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Nano moles
Cycle 1 Day 1 Predose	Number Analyzed	207 participants	69 participants
		NA [1]; (NA%)	NA [1]; (NA%)
Cycle 1 Day 1-0.5 - 2 hours	Number Analyzed	207 participants	69 participants
		0.1542; (230.5161%)	NA [1]; (NA%)
Cycle 1 Day 1-3 - 5 hours	Number Analyzed	223 participants	69 participants
		3.9399; (153.7651%)	6.3053; (123.9308%)
Cycle 3 Day 1-Predose	Number Analyzed	183 participants	67 participants
		42.9123; (50.2410%)	56.8319; (51.0378%)
Cycle 3 Day 1, 0.5 - 2 hours	Number Analyzed	183 participants	68 participants
		42.7434; (52.8557%)	55.9947; (59.1318%)
Cycle 3 Day 1, 3 - 5 hours	Number Analyzed	182 participants	67 participants
		48.3547; (50.4286%)	64.0621; (54.2058%)
Cycle 5 Day 1, Predose	Number Analyzed	181 participants	67 participants
		39.3718; (56.6226%)	56.0330; (57.5022%)
Cycle 5 Day 1, 0.5 - 2 hours	Number Analyzed	178 participants	67 participants
		39.4145; (55.3468%)	55.3767; (55.9096%)
Cycle 5 Day 1, 3-5 hours	Number Analyzed	180 participants	67 participants
		45.6842; (54.3876%)	63.9216; (56.4249%)
Cycle 7 Day 1- Predose	Number Analyzed	181 participants	62 participants
		38.3847; (50.0861%)	52.5786; (51.0588%)
Cycle 7 Day 1, 0.5-2 hours	Number Analyzed	179 participants	61 participants
		38.5301; (49.6296%)	52.7638; (47.4797%)
Cycle 7 Day 1, 3-5 hours	Number Analyzed	179 participants	62 participants
		44.4670; (48.4730%)	60.6201; (50.6931%)
Cycle 9 Day 1, Predose	Number Analyzed	165 participants	62 participants
		40.1230; (47.0682%)	54.4349; (51.3447%)
Cycle 9 Day 1, 0.5-2 hours	Number Analyzed	165 participants	61 participants
		40.4987; (47.6483%)	54.7158; (54.6783%)
Cycle 9 Day 1, 3-5 hours	Number Analyzed	163 participants	62 participants
		46.0310; (44.6875%)	60.4649; (52.6147%)
Cycle 11 Day 1, Predose	Number Analyzed	158 participants	59 participants
		38.3859; (48.5351%)	56.4782; (59.1303%)
Cycle 11 Day 1, 0.5-2 hours	Number Analyzed	160 participants	59 participants
		38.7620; (48.1414%)	57.4095; (57.0891%)
Cycle 11 Day 1, 3-5 hours	Number Analyzed	161 participants	59 participants
		43.9135; (50.6779%)	65.1943; (58.5043%)
Cycle 13 Day 1, Predose	Number Analyzed	150 participants	55 participants
		40.4356; (47.2671%)	55.1162; (54.3493%)
Cycle 13 Day 1, 0.5- 2 hours	Number Analyzed	147 participants	54 participants
		40.1116; (46.3929%)	54.3858; (49.9148%)
Cycle 13 Day 1, 3-5 hours	Number Analyzed	147 participants	55 participants
		45.9083; (44.8309%)	61.7426; (51.2924%)

[1]

NA as the values were non-quantifiable and not calculable

10. Secondary Outcome

Title	Plasma Concentrations of Metabolite AZ7550
Description	To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ7550.
Time Frame	Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis set (osimertinib arm only) was defined as participants in the FAS who had at least 1 evaluable PK concentration and who had no detectable pre-dose osimertinib concentrations above the lower limit of quantitation (LLQ) on Cycle 1 Day 1.

Arm/Group Title		Osimertinib 80 mg (Global Cohort)	Osimertinib 80 mg (China Cohort)
Arm/Group Description:		Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participants received Osimertinib 80 mg orally once daily (QD)
Overall Number of Participants Analyzed		279	71
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Nano moles
Cycle 1 Day 1, Predose	Number Analyzed	207 participants	69 participants
		NA [1]; (NA%)	NA [1]; (NA%)
Cycle 1 Day 1, 0.5 - 2 hours	Number Analyzed	207 participants	69 participants
		0.1437; (168.2087%)	NA [1]; (NA%)
Cycle 1 Day 1, 3 - 5 hours	Number Analyzed	219 participants	66 participants
		1.8610; (147.4624%)	2.1876; (123.6012%)
Cycle 3 Day 1, Predose	Number Analyzed	183 participants	67 participants
		46.1286; (45.1082%)	55.9958; (50.5705%)
Cycle 3 Day 1, 0.5 - 2 hours	Number Analyzed	183 participants	68 participants
		46.0045; (45.9584%)	55.6754; (53.0925%)
Cycle 3 Day 1, 3 - 5 hours	Number Analyzed	182 participants	67 participants
		51.7182; (45.3240%)	62.3493; (53.5513%)
Cycle 5 Day 1, Predose	Number Analyzed	181 participants	67 participants
		44.4537; (54.9882%)	53.0434; (52.2936%)
Cycle 5 Day 1, 0.5 - 2 hours	Number Analyzed	178 participants	67 participants
		45.2186; (51.6418%)	53.1901; (51.5506%)
Cycle 5 Day 1, 3-5 hours	Number Analyzed	180 participants	67 participants
		51.4018; (51.3627%)	62.5218; (51.0627%)
Cycle 7 Day 1, Predose	Number Analyzed	181 participants	62 participants
		46.2912; (49.8713%)	53.4167; (50.8399%)
Cycle 7 Day 1, 0.5-2 hours	Number Analyzed	179 participants	61 participants
		46.3540; (49.0845%)	54.3942; (46.1253%)
Cycle 7 Day 1,3-5 hours	Number Analyzed	179 participants	62 participants
		52.3533; (47.6489%)	61.9004; (51.6117%)
Cycle 9 Day 1, Predose	Number Analyzed	165 participants	62 participants
		49.6058; (45.5050%)	54.8207; (50.2534%)
Cycle 9 Day 1, 0.5-2 hours	Number Analyzed	165 participants	61 participants
		49.9381; (46.4568%)	55.2437; (52.5736%)
Cycle 9 Day 1, 3-5 hours	Number Analyzed	163 participants	62 participants
		56.5354; (45.6736%)	60.8933; (50.3474%)
Cycle 11 Day 1, Predose	Number Analyzed	158 participants	59 participants
		50.9710; (46.8840%)	56.4643; (51.2351%)
Cycle 11 Day 1, 0.5- 2 hours	Number Analyzed	160 participants	59 participants
		51.9773; (45.3186%)	57.4778; (47.3639%)
Cycle 11 Day 1, 3- 5 hours	Number Analyzed	161 participants	59 participants
		57.6986; (48.2382%)	65.3053; (49.6916%)
Cycle 13 Day 1, Predose	Number Analyzed	150 participants	55 participants
		54.5238; (43.8481%)	56.0666; (51.2464%)
Cycle 13 Day 1, 0.5-2 hours	Number Analyzed	146 participants	54 participants
		54.1224; (43.7869%)	56.8750; (47.4338%)
Cycle 13 Day 1, 3-5 hours	Number Analyzed	146 participants	55 participants
		61.6053; (42.2947%)	63.3365; (46.3082%)

[1]

NA as the values are not calculable and non-quantifiable.

11. Secondary Outcome

Title	Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire)
Description	The CTSQ-16 was a 16-item questionnaire measuring 3 domains related to participant's satisfaction with cancer therapy: Expectations of therapy, Feelings about side effects, and Satisfaction with therapy. Scores ranged from 0 to 100 for each domain, with a higher score associated with the best outcome on each domain. The three domains of interest were separately analysed using an ANCOVA stratified by race (Asian versus Non-Asian) and mutation type (Ex19del versus L858R). The results of the analyses were presented in terms of mean together with standard deviation.
Time Frame	Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months)

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title		Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:		Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed		279	277	71	65
Mean (Standard Deviation); Unit of Measure: Unit on scale
Expectations with Therapy, Week 3	Number Analyzed	227 participants	216 participants	59 participants	60 participants
		74.1 (22.42)	70.3 (21.85)	77.1 (20.60)	79.2 (18.58)
Expectations with Therapy, Week 6	Number Analyzed	222 participants	210 participants	60 participants	55 participants
		76.3 (20.58)	74.0 (19.46)	82.2 (17.88)	82.6 (17.95)
Feelings about Side-Effects, Week 3	Number Analyzed	227 participants	216 participants	59 participants	60 participants
		74.5 (17.22)	69.1 (20.96)	73.3 (19.89)	72.5 (17.46)
Feelings about Side-Effects, Week 6	Number Analyzed	222 participants	210 participants	60 participants	55 participants
		74.6 (19.83)	69.9 (20.73)	69.0 (24.46)	69.7 (20.99)
Satisfaction with Therapy, Week 3	Number Analyzed	227 participants	216 participants	59 participants	60 participants
		84.4 (12.88)	82.6 (13.60)	87.2 (12.14)	86.6 (11.07)
Satisfaction with Therapy, Week 6	Number Analyzed	222 participants	210 participants	60 participants	55 participants
		84.2 (13.94)	84.6 (12.38)	87.4 (13.29)	87.2 (12.06)

12. Secondary Outcome

Title	Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13)
Description	The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Time Frame	Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title		Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:		Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed		279	277	71	65
Least Squares Mean (95% Confidence Interval); Unit of Measure: Unit on scale
Dyspnoea, First 9 months	Number Analyzed	248 participants	252 participants	67 participants	57 participants
		-4.04; (-5.63 to -2.45)	-4.14; (-5.73 to -2.54)	-4.87; (-7.81 to -1.92)	-4.82; (-8.01 to -1.63)
Dyspnoea, week 1	Number Analyzed	241 participants	246 participants	67 participants	57 participants
		-3.46; (-5.12 to -1.81)	-3.60; (-5.24 to -1.96)	-1.61; (-5.03 to 1.81)	0.68; (-3.03 to 4.39)
Dyspnoea, week 2	Number Analyzed	236 participants	236 participants	66 participants	57 participants
		-3.94; (-5.87 to -2.00)	-3.64; (-5.57 to -1.70)	-2.27; (-6.01 to 1.48)	-5.03; (-9.08 to -0.98)
Dyspnoea, week 3	Number Analyzed	239 participants	237 participants	63 participants	57 participants
		-3.99; (-5.85 to -2.12)	-3.27; (-5.14 to -1.41)	-3.09; (-6.96 to 0.77)	-5.55; (-9.69 to -1.42)
Dyspnoea, week 4	Number Analyzed	206 participants	211 participants	63 participants	53 participants
		-4.81; (-6.59 to -3.02)	-4.11; (-5.88 to -2.34)	-5.35; (-8.72 to -1.99)	-5.55; (-9.20 to -1.89)
Dyspnoea, week 5	Number Analyzed	199 participants	196 participants	57 participants	55 participants
		-3.51; (-5.53 to -1.50)	-5.19; (-7.22 to -3.17)	-5.72; (-10.06 to -1.39)	-5.76; (-10.32 to -1.20)
Dyspnoea, week 6	Number Analyzed	222 participants	214 participants	64 participants	53 participants
		-4.51; (-6.47 to -2.56)	-4.45; (-6.42 to -2.48)	-4.83; (-8.53 to -1.12)	-6.37; (-10.40 to -2.33)
Dyspnoea, week 12	Number Analyzed	225 participants	203 participants	61 participants	52 participants
		-3.83; (-5.99 to -1.68)	-5.75; (-7.96 to -3.54)	-5.38; (-9.41 to -1.35)	-6.67; (-11.04 to -2.30)
Dyspnoea, week 18	Number Analyzed	214 participants	199 participants	59 participants	52 participants
		-4.97; (-7.18 to -2.76)	-5.21; (-7.46 to -2.95)	-7.67; (-11.54 to -3.79)	-7.48; (-11.66 to -3.30)
Dyspnoea, week 24	Number Analyzed	202 participants	185 participants	55 participants	47 participants
		-4.65; (-7.06 to -2.25)	-4.56; (-7.02 to -2.09)	-7.59; (-11.84 to -3.34)	-5.67; (-10.27 to -1.08)
Dyspnoea, week 30	Number Analyzed	195 participants	172 participants	55 participants	49 participants
		-3.89; (-6.34 to -1.45)	-3.68; (-6.22 to -1.15)	-5.81; (-10.59 to -1.02)	-3.46; (-8.58 to 1.65)
Dyspnoea, week 36	Number Analyzed	184 participants	151 participants	52 participants	43 participants
		-2.88; (-5.52 to -0.24)	-2.04; (-4.83 to 0.75)	-4.21; (-8.91 to 0.48)	-2.18; (-7.28 to 2.93)
Cough, First 9 months	Number Analyzed	248 participants	252 participants	67 participants	57 participants
		-10.97; (-12.77 to -9.17)	-11.65; (-13.47 to -9.84)	-13.75; (-17.17 to -10.33)	-8.49; (-12.19 to -4.79)
Cough, week 1	Number Analyzed	241 participants	246 participants	67 participants	57 participants
		-6.90; (-9.30 to -4.51)	-4.83; (-7.20 to -2.46)	-4.60; (-9.00 to -0.20)	-3.69; (-8.46 to 1.07)
Cough, week 2	Number Analyzed	236 participants	236 participants	66 participants	57 participants
		-9.04; (-11.58 to -6.49)	-9.52; (-12.05 to -6.98)	-12.26; (-17.15 to -7.37)	-3.73; (-9.01 to 1.54)
Cough, week 3	Number Analyzed	239 participants	237 participants	63 participants	57 participants
		-9.78; (-12.37 to -7.20)	-10.24; (-12.82 to -7.65)	-11.95; (-16.66 to -7.24)	-5.56; (-10.57 to -0.54)
Cough, week 4	Number Analyzed	206 participants	211 participants	63 participants	53 participants
		-11.25; (-13.87 to -8.63)	-13.36; (-15.96 to -10.76)	-12.78; (-17.80 to -7.77)	-10.32; (-15.75 to -4.90)
Cough, week 5	Number Analyzed	199 participants	196 participants	57 participants	55 participants
		-12.98; (-15.64 to -10.31)	-13.55; (-16.21 to -10.88)	-17.74; (-23.11 to -12.38)	-9.20; (-14.84 to -3.55)
Cough, week 6	Number Analyzed	222 participants	214 participants	64 participants	53 participants
		-11.88; (-14.56 to -9.19)	-11.92; (-14.63 to -9.21)	-16.92; (-22.36 to -11.48)	-10.58; (-16.52 to -4.64)
Cough, week 12	Number Analyzed	225 participants	203 participants	61 participants	52 participants
		-13.36; (-15.95 to -10.78)	-13.57; (-16.24 to -10.90)	-15.51; (-21.39 to -9.64)	-8.04; (-14.41 to -1.67)
Cough, week 18	Number Analyzed	214 participants	199 participants	59 participants	52 participants
		-12.31; (-15.25 to -9.37)	-11.00; (-14.03 to -7.98)	-11.79; (-17.19 to -6.40)	-9.44; (-15.23 to -3.65)
Cough, week 24	Number Analyzed	202 participants	185 participants	55 participants	47 participants
		-11.34; (-14.24 to -8.43)	-13.16; (-16.17 to -10.14)	-17.61; (-22.84 to -12.39)	-14.92; (-20.56 to -9.29)
Cough, week 30	Number Analyzed	195 participants	172 participants	55 participants	49 participants
		-10.34; (-13.21 to -7.46)	-12.43; (-15.44 to -9.41)	-15.45; (-21.46 to -9.45)	-9.35; (-15.75 to -2.94)
Cough, week 36	Number Analyzed	184 participants	151 participants	52 participants	43 participants
		-11.49; (-14.48 to -8.49)	-14.62; (-17.85 to -11.39)	-14.62; (-20.65 to -8.58)	-8.55; (-15.14 to -1.96)
Pain in Chest, First 9 months	Number Analyzed	248 participants	252 participants	67 participants	57 participants
		-6.62; (-8.24 to -5.01)	-6.41; (-8.04 to -4.78)	-2.79; (-5.84 to 0.26)	-4.74; (-8.05 to -1.44)
Pain in Chest, week 1	Number Analyzed	241 participants	246 participants	67 participants	57 participants
		-1.93; (-4.19 to 0.32)	-4.26; (-6.50 to -2.03)	-1.79; (-5.98 to 2.40)	-4.16; (-8.71 to 0.38)
Pain in Chest, week 2	Number Analyzed	236 participants	236 participants	66 participants	57 participants
		-5.94; (-8.13 to -3.74)	-6.32; (-8.51 to -4.13)	-4.76; (-8.63 to -0.89)	-3.00; (-7.18 to 1.17)
Pain in Chest, week 3	Number Analyzed	239 participants	237 participants	63 participants	57 participants
		-7.17; (-9.31 to -5.04)	-5.36; (-7.49 to -3.23)	-0.76; (-4.90 to 3.39)	-4.77; (-9.18 to -0.36)
Pain in Chest, week 4	Number Analyzed	206 participants	211 participants	63 participants	53 participants
		-7.45; (-9.60 to -5.29)	-6.40; (-8.54 to -4.26)	-2.13; (-6.32 to 2.07)	-4.22; (-8.78 to 0.34)
Pain in Chest, week 5	Number Analyzed	199 participants	196 participants	57 participants	55 participants
		-7.33; (-9.54 to -5.11)	-6.98; (-9.20 to -4.76)	-0.62; (-4.67 to 3.42)	-6.82; (-11.05 to -2.60)
Pain in Chest, week 6	Number Analyzed	222 participants	214 participants	64 participants	53 participants
		-4.99; (-7.30 to -2.68)	-7.08; (-9.41 to -4.75)	0.94; (-3.40 to 5.29)	-6.26; (-11.00 to -1.52)
Pain in Chest, week 12	Number Analyzed	225 participants	203 participants	61 participants	52 participants
		-7.28; (-9.56 to -5.01)	-6.70; (-9.05 to -4.35)	-3.71; (-8.77 to 1.35)	-5.13; (-10.62 to 0.36)
Pain in Chest, week 18	Number Analyzed	214 participants	199 participants	59 participants	52 participants
		-6.79; (-9.22 to -4.36)	-7.90; (-10.40 to -5.41)	-4.40; (-9.05 to 0.26)	-7.24; (-12.23 to -2.25)
Pain in Chest, week 24	Number Analyzed	202 participants	185 participants	55 participants	47 participants
		-7.72; (-10.26 to -5.18)	-7.34; (-9.95 to -4.72)	-5.66; (-10.48 to -0.84)	-3.15; (-8.36 to 2.07)
Pain in Chest, week 30	Number Analyzed	195 participants	172 participants	55 participants	49 participants
		-8.33; (-10.80 to -5.87)	-6.60; (-9.18 to -4.02)	-4.25; (-9.62 to 1.12)	-4.02; (-9.76 to 1.72)
Pain in Chest, week 36	Number Analyzed	184 participants	151 participants	52 participants	43 participants
		-7.94; (-10.59 to -5.30)	-5.58; (-8.43 to -2.73)	-3.56; (-9.42 to 2.30)	-3.40; (-9.80 to 3.00)

13. Secondary Outcome

Title	Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30)
Description	The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, combined to produce 5 functional scales, 3 symptom scales, 6 individual items, and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Time Frame	Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36.

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.

Arm/Group Title		Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description:		Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed		279	277	71	65
Least Squares Mean (95% Confidence Interval); Unit of Measure: Unit on scale
Fatigue, First 9 months	Number Analyzed	252 participants	247 participants	68 participants	63 participants
		-5.48; (-7.45 to -3.52)	-4.72; (-6.74 to -2.69)	-5.65; (-9.33 to -1.98)	-5.79; (-9.58 to -2.00)
Fatigue, week 6	Number Analyzed	239 participants	236 participants	68 participants	63 participants
		-4.13; (-6.35 to -1.91)	-5.78; (-8.02 to -3.54)	-1.73; (-6.05 to 2.58)	-6.81; (-11.30 to -2.33)
Fatigue, week 12	Number Analyzed	237 participants	210 participants	65 participants	61 participants
		-5.11; (-7.31 to -2.91)	-6.52; (-8.81 to -4.23)	-5.40; (-9.51 to -1.29)	-6.36; (-10.61 to -2.12)
Fatigue, week 18	Number Analyzed	229 participants	214 participants	61 participants	60 participants
		-6.83; (-9.21 to -4.44)	-5.77; (-8.23 to -3.31)	-6.64; (-11.26 to -2.03)	-7.90; (-12.61 to -3.19)
Fatigue, week 24	Number Analyzed	216 participants	195 participants	57 participants	57 participants
		-6.18; (-8.75 to -3.61)	-4.96; (-7.63 to -2.28)	-8.92; (-13.30 to -4.54)	-3.87; (-8.32 to 0.58)
Fatigue, week 30	Number Analyzed	207 participants	178 participants	57 participants	56 participants
		-5.19; (-7.94 to -2.43)	-3.26; (-6.16 to -0.35)	-4.43; (-9.53 to 0.68)	-6.31; (-11.53 to -1.10)
Fatigue, week 36	Number Analyzed	193 participants	158 participants	55 participants	50 participants
		-5.47; (-8.31 to -2.63)	-2.00; (-2.00 to 1.04)	-6.78; (-12.38 to -1.19)	-3.46; (-9.28 to 2.36)
Appetite Loss, First 9 months	Number Analyzed	252 participants	247 participants	68 participants	63 participants
		-6.15; (-8.39 to -3.90)	-5.64; (-7.96 to -3.32)	1.18; (-2.78 to 5.14)	-1.73; (-5.80 to 2.34)
Appetite Loss, week 6	Number Analyzed	239 participants	236 participants	68 participants	63 participants
		-4.54; (-7.36 to -1.72)	-5.67; (-8.52 to -2.83)	3.20; (-1.60 to 8.01)	-6.27; (-11.26 to -1.27)
Appetite Loss, week 12	Number Analyzed	237 participants	210 participants	65 participants	61 participants
		-6.52; (-9.43 to -3.62)	-6.95; (-9.98 to -3.91)	1.58; (-3.23 to 6.39)	-1.44; (-6.41 to 3.53)
Appetite Loss, week 18	Number Analyzed	229 participants	214 participants	61 participants	60 participants
		-7.27; (-10.09 to -4.45)	-6.84; (-9.75 to -3.92)	1.42; (-4.38 to 7.22)	-4.43; (-10.35 to 1.48)
Appetite Loss, week 24	Number Analyzed	216 participants	195 participants	57 participants	57 participants
		-7.14; (-10.27 to -4.01)	-5.08; (-8.35 to -1.81)	-2.26; (-7.74 to 3.22)	0.24; (-5.29 to 5.78)
Appetite Loss, week 30	Number Analyzed	207 participants	178 participants	57 participants	56 participants
		-4.50; (-7.74 to -1.26)	-4.17; (-7.60 to -0.74)	2.19; (-3.28 to 7.65)	-1.83; (-7.36 to 3.70)
Appetite Loss, week 36	Number Analyzed	193 participants	158 participants	55 participants	50 participants
		-6.90; (-10.00 to -3.81)	-5.15; (-8.49 to -1.81)	0.98; (-5.28 to 7.24)	3.36; (-3.15 to 9.86)

Adverse Events

Time Frame	All adverse events (AEs) were collected from the time of signature of informed consent throughout the Treatment Period and including the safety follow-up period.The safety follow-up period was defined as 28 days after study drug was discontinued
Adverse Event Reporting Description	An adverse event was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. In clinical studies, an AE included an undesirable medical condition occurring at any time, including run-in or washout periods, even if no study treatment had been administered. The term AE was used to include both serious and non-serious AEs.
Arm/Group Title	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
Arm/Group Description	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.	Randomized participants received Osimertinib 80 mg orally once daily (QD)	Randomized participant received Standard of care (SoC) Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI). Participants received gefitinib 250 mg orally QD or erlotinib 150 mg orally QD.
All-Cause Mortality
	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	155/279 (55.56%)	166/277 (59.93%)	45/71 (63.38%)	44/65 (67.69%)
Serious Adverse Events
	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	74/279 (26.52%)	76/277 (27.44%)	25/71 (35.21%)	12/65 (18.46%)
Blood and lymphatic system disorders
Anaemia * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pancytopenia * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Blood disorder * 1	0/279 (0.00%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Neutropenia * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Cardiac disorders
Acute myocardial infarction * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Angina pectoris * 1	1/279 (0.36%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Atrial fibrillation * 1	1/279 (0.36%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Bundle branch block left * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Cardiac arrest * 1	1/279 (0.36%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Cardiac failure * 1	1/279 (0.36%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Cardiac tamponade * 1	1/279 (0.36%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Myocardial infarction * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Tachyarrhythmia * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Cardiac failure * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Pericardial effusion * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Ear and labyrinth disorders
Vertigo * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Gastrointestinal disorders
Abdominal pain * 1	2/279 (0.72%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Chronic gastritis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Diarrhoea * 1	3/279 (1.08%)	4/277 (1.44%)	0/71 (0.00%)	0/65 (0.00%)
Enterocolitis * 1	2/279 (0.72%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Gastritis erosive * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Gastrointestinal haemorrhage * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Haemorrhoidal haemorrhage * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Inguinal hernia * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Intestinal ischaemia * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Melaena * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Mouth ulceration * 1	0/279 (0.00%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Stomatitis * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Vomiting * 1	1/279 (0.36%)	5/277 (1.81%)	0/71 (0.00%)	0/65 (0.00%)
Duodenal ulcer * 1	0/279 (0.00%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Upper gastrointestinal haemorrhage * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
General disorders
Asthenia * 1	2/279 (0.72%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Chest pain * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Condition aggravated * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Death * 1	0/279 (0.00%)	1/277 (0.36%)	1/71 (1.41%)	0/65 (0.00%)
Drug withdrawal syndrome * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Fatigue * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
General physical health deterioration * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pyrexia * 1	3/279 (1.08%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Hepatobiliary disorders
Drug-induced liver injury * 1	0/279 (0.00%)	3/277 (1.08%)	0/71 (0.00%)	0/65 (0.00%)
Cholecystitis * 1	0/279 (0.00%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Hepatic function abnormal * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Hepatitis C * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Infections and infestations
Anal abscess * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Bacteraemia * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Clostridial infection * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Clostridium difficile infection * 1	1/279 (0.36%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Cystitis * 1	0/279 (0.00%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Device related infection * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Diarrhoea infectious * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Diverticulitis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Empyema * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Endocarditis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Enteritis infectious * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Escherichia urinary tract infection * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Febrile infection * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Gastroenteritis * 1	2/279 (0.72%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Lower respiratory tract infection * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Lower respiratory tract infection viral * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Perineal abscess * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pharyngotonsillitis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pleural infection * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pneumonia * 1	9/279 (3.23%)	7/277 (2.53%)	3/71 (4.23%)	1/65 (1.54%)
Pneumonia mycoplasmal * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Rectal abscess * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Respiratory tract infection * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Salmonella bacteraemia * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Sepsis * 1	3/279 (1.08%)	3/277 (1.08%)	0/71 (0.00%)	0/65 (0.00%)
Sinusitis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Tracheobronchitis * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Urinary tract infection * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Bronchitis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Adenoviral upper respiratory infection * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Lung infection * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Upper respiratory tract infection * 1	0/279 (0.00%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Injury, poisoning and procedural complications
Fall * 1	1/279 (0.36%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Femoral neck fracture * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Femur fracture * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Head injury * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Procedural pneumothorax * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Subarachnoid haemorrhage * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Subdural haematoma * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Wound complication * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Wrist fracture * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Poisoning * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Investigations
Alanine aminotransferase increased * 1	1/279 (0.36%)	2/277 (0.72%)	1/71 (1.41%)	1/65 (1.54%)
Aspartate aminotransferase increased * 1	1/279 (0.36%)	1/277 (0.36%)	1/71 (1.41%)	0/65 (0.00%)
Electrocardiogram QT prolonged * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Platelet count decreased * 1	1/279 (0.36%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Transaminases increased * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Blood bilirubin increased * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
White blood cell count decreased * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Metabolism and nutrition disorders
Decreased appetite * 1	2/279 (0.72%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Diabetic ketoacidosis * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Hyperglycaemia * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Hypoglycaemia * 1	0/279 (0.00%)	1/277 (0.36%)	1/71 (1.41%)	0/65 (0.00%)
Hyponatraemia * 1	4/279 (1.43%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Hyperuricaemia * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Tumour lysis syndrome * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Flank pain * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Musculoskeletal chest pain * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pathological fracture * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Rotator cuff syndrome * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Bone pain * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	1/65 (1.54%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Histiocytic necrotising lymphadenitis * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Invasive ductal breast carcinoma * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Ovarian fibroma * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Prostate cancer * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Uterine leiomyoma * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Nervous system disorders
Brain oedema * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Cerebral infarction * 1	1/279 (0.36%)	1/277 (0.36%)	1/71 (1.41%)	0/65 (0.00%)
Cerebrovascular accident * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Cognitive disorder * 1	1/279 (0.36%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Depressed level of consciousness * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Dizziness * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Haemorrhagic stroke * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Ischaemic stroke * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Migraine * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Peripheral motor neuropathy * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Seizure * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Spinal cord compression * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Transient ischaemic attack * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Cerebral ventricle dilatation * 1	0/279 (0.00%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Epilepsy * 1	0/279 (0.00%)	0/277 (0.00%)	0/71 (0.00%)	1/65 (1.54%)
Psychiatric disorders
Acute psychosis * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Confusional state * 1	1/279 (0.36%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Depression * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Renal and urinary disorders
Acute kidney injury * 1	2/279 (0.72%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Renal failure * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Ureterolithiasis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Reproductive system and breast disorders
Uterine polyp * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Dyspnoea * 1	2/279 (0.72%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Haemoptysis * 1	0/279 (0.00%)	4/277 (1.44%)	0/71 (0.00%)	1/65 (1.54%)
Hypoxia * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Interstitial lung disease * 1	4/279 (1.43%)	3/277 (1.08%)	1/71 (1.41%)	1/65 (1.54%)
Pleural effusion * 1	3/279 (1.08%)	3/277 (1.08%)	3/71 (4.23%)	1/65 (1.54%)
Pneumonitis * 1	2/279 (0.72%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pneumothorax * 1	2/279 (0.72%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Pulmonary embolism * 1	4/279 (1.43%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Pulmonary haemorrhage * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Respiratory failure * 1	0/279 (0.00%)	2/277 (0.72%)	1/71 (1.41%)	0/65 (0.00%)
Tonsillolith * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Bronchiectasis * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform * 1	0/279 (0.00%)	2/277 (0.72%)	0/71 (0.00%)	0/65 (0.00%)
Toxic epidermal necrolysis * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Vascular disorders
Aortic dissection * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Circulatory collapse * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Deep vein thrombosis * 1	2/279 (0.72%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
Embolism * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Orthostatic hypotension * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Peripheral artery occlusion * 1	0/279 (0.00%)	1/277 (0.36%)	0/71 (0.00%)	0/65 (0.00%)
Thrombophlebitis * 1	1/279 (0.36%)	0/277 (0.00%)	0/71 (0.00%)	0/65 (0.00%)
Venous thrombosis limb * 1	0/279 (0.00%)	0/277 (0.00%)	1/71 (1.41%)	0/65 (0.00%)
1 Term from vocabulary, 20.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Osimertinib 80 mg (Global Cohort)	SoC EGFR-TKI (Global Cohort)	Osimertinib 80 mg (China Cohort)	SoC EGFR-TKI (China Cohort)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	273/279 (97.85%)	271/277 (97.83%)	70/71 (98.59%)	64/65 (98.46%)
Blood and lymphatic system disorders
Anaemia * 1	44/279 (15.77%)	27/277 (9.75%)	27/71 (38.03%)	11/65 (16.92%)
Thrombocytopenia * 1	26/279 (9.32%)	0/277 (0.00%)	7/71 (9.86%)	1/65 (1.54%)
Leukopenia * 1	21/279 (7.53%)	3/277 (1.08%)	12/71 (16.90%)	2/65 (3.08%)
Neutropenia * 1	21/279 (7.53%)	1/277 (0.36%)	12/71 (16.90%)	2/65 (3.08%)
Cardiac disorders
Left ventricular dysfunction * 1	0/279 (0.00%)	0/277 (0.00%)	2/71 (2.82%)	5/65 (7.69%)
Eye disorders
Dry eye * 1	21/279 (7.53%)	21/277 (7.58%)	0/71 (0.00%)	0/65 (0.00%)
Gastrointestinal disorders
Diarrhoea * 1	167/279 (59.86%)	162/277 (58.48%)	17/71 (23.94%)	19/65 (29.23%)
Stomatitis * 1	82/279 (29.39%)	60/277 (21.66%)	0/71 (0.00%)	0/65 (0.00%)
Nausea * 1	55/279 (19.71%)	55/277 (19.86%)	10/71 (14.08%)	7/65 (10.77%)
Constipation * 1	51/279 (18.28%)	39/277 (14.08%)	4/71 (5.63%)	3/65 (4.62%)
Vomiting * 1	41/279 (14.70%)	32/277 (11.55%)	10/71 (14.08%)	5/65 (7.69%)
Dry mouth * 1	12/279 (4.30%)	15/277 (5.42%)	0/71 (0.00%)	0/65 (0.00%)
Abdominal pain * 1	14/279 (5.02%)	17/277 (6.14%)	0/71 (0.00%)	0/65 (0.00%)
Mouth ulceration * 1	0/279 (0.00%)	0/277 (0.00%)	12/71 (16.90%)	7/65 (10.77%)
Toothache * 1	0/279 (0.00%)	0/277 (0.00%)	0/71 (0.00%)	4/65 (6.15%)
General disorders
Fatigue * 1	45/279 (16.13%)	35/277 (12.64%)	7/71 (9.86%)	6/65 (9.23%)
Pyrexia * 1	32/279 (11.47%)	12/277 (4.33%)	0/71 (0.00%)	0/65 (0.00%)
Oedema peripheral * 1	16/279 (5.73%)	24/277 (8.66%)	0/71 (0.00%)	0/65 (0.00%)
Asthenia * 1	27/279 (9.68%)	10/277 (3.61%)	5/71 (7.04%)	3/65 (4.62%)
Chest discomfort * 1	0/279 (0.00%)	0/277 (0.00%)	6/71 (8.45%)	8/65 (12.31%)
Non-cardiac chest pain * 1	18/279 (6.45%)	17/277 (6.14%)	8/71 (11.27%)	5/65 (7.69%)
Hepatobiliary disorders
Hepatic function abnormal * 1	0/279 (0.00%)	0/277 (0.00%)	2/71 (2.82%)	5/65 (7.69%)
Drug-induced liver injury * 1	0/279 (0.00%)	0/277 (0.00%)	2/71 (2.82%)	6/65 (9.23%)
Infections and infestations
Paronychia * 1	89/279 (31.90%)	84/277 (30.32%)	9/71 (12.68%)	2/65 (3.08%)
Upper respiratory tract infection * 1	36/279 (12.90%)	23/277 (8.30%)	9/71 (12.68%)	3/65 (4.62%)
Conjunctivitis * 1	18/279 (6.45%)	21/277 (7.58%)	1/71 (1.41%)	4/65 (6.15%)
Pneumonia * 1	24/279 (8.60%)	11/277 (3.97%)	5/71 (7.04%)	3/65 (4.62%)
Urinary tract infection * 1	17/279 (6.09%)	12/277 (4.33%)	8/71 (11.27%)	8/65 (12.31%)
Urinary tract infection bacterial * 1	0/279 (0.00%)	0/277 (0.00%)	5/71 (7.04%)	4/65 (6.15%)
Investigations
Aspartate aminotransferase increased * 1	28/279 (10.04%)	69/277 (24.91%)	11/71 (15.49%)	28/65 (43.08%)
Alanine aminotransferase increased * 1	19/279 (6.81%)	74/277 (26.71%)	6/71 (8.45%)	29/65 (44.62%)
Electrocardiogram QT prolonged * 1	28/279 (10.04%)	12/277 (4.33%)	6/71 (8.45%)	3/65 (4.62%)
Weight decreased * 1	20/279 (7.17%)	20/277 (7.22%)	17/71 (23.94%)	8/65 (12.31%)
White blood cell count decreased * 1	27/279 (9.68%)	5/277 (1.81%)	29/71 (40.85%)	6/65 (9.23%)
Blood alkaline phosphatase increased * 1	7/279 (2.51%)	15/277 (5.42%)	6/71 (8.45%)	4/65 (6.15%)
Platelet count decreased * 1	15/279 (5.38%)	4/277 (1.44%)	20/71 (28.17%)	1/65 (1.54%)
Neutrophil count decreased * 1	0/279 (0.00%)	0/277 (0.00%)	17/71 (23.94%)	3/65 (4.62%)
Lymphocyte count decreased * 1	0/279 (0.00%)	0/277 (0.00%)	11/71 (15.49%)	3/65 (4.62%)
Gamma-glutamyltransferase increased * 1	0/279 (0.00%)	0/277 (0.00%)	6/71 (8.45%)	7/65 (10.77%)
Blood bilirubin increased * 1	0/279 (0.00%)	0/277 (0.00%)	3/71 (4.23%)	6/65 (9.23%)
Blood albumin decreased * 1	0/279 (0.00%)	0/277 (0.00%)	5/71 (7.04%)	3/65 (4.62%)
Blood creatinine increased * 1	0/279 (0.00%)	0/277 (0.00%)	5/71 (7.04%)	2/65 (3.08%)
Blood lactate dehydrogenase increased * 1	0/279 (0.00%)	0/277 (0.00%)	5/71 (7.04%)	2/65 (3.08%)
Haemoglobin decreased * 1	0/279 (0.00%)	0/277 (0.00%)	2/71 (2.82%)	4/65 (6.15%)
Blood uric acid increased * 1	0/279 (0.00%)	0/277 (0.00%)	4/71 (5.63%)	1/65 (1.54%)
Metabolism and nutrition disorders
Decreased appetite * 1	66/279 (23.66%)	58/277 (20.94%)	10/71 (14.08%)	8/65 (12.31%)
Hypokalaemia * 1	13/279 (4.66%)	19/277 (6.86%)	12/71 (16.90%)	8/65 (12.31%)
Hypoalbuminaemia * 1	0/279 (0.00%)	0/277 (0.00%)	12/71 (16.90%)	6/65 (9.23%)
Hypocalcaemia * 1	0/279 (0.00%)	0/277 (0.00%)	7/71 (9.86%)	7/65 (10.77%)
Hyponatraemia * 1	17/279 (6.09%)	10/277 (3.61%)	9/71 (12.68%)	0/65 (0.00%)
Hypoproteinaemia * 1	0/279 (0.00%)	0/277 (0.00%)	5/71 (7.04%)	3/65 (4.62%)
Hyperglycaemia * 1	0/279 (0.00%)	0/277 (0.00%)	4/71 (5.63%)	2/65 (3.08%)
Musculoskeletal and connective tissue disorders
Back pain * 1	36/279 (12.90%)	29/277 (10.47%)	7/71 (9.86%)	6/65 (9.23%)
Arthralgia * 1	23/279 (8.24%)	21/277 (7.58%)	0/71 (0.00%)	0/65 (0.00%)
Musculoskeletal pain * 1	28/279 (10.04%)	14/277 (5.05%)	0/71 (0.00%)	0/65 (0.00%)
Myalgia * 1	19/279 (6.81%)	14/277 (5.05%)	0/71 (0.00%)	0/65 (0.00%)
Muscle spasms * 1	24/279 (8.60%)	13/277 (4.69%)	0/71 (0.00%)	0/65 (0.00%)
Pain in extremity * 1	19/279 (6.81%)	6/277 (2.17%)	7/71 (9.86%)	3/65 (4.62%)
Nervous system disorders
Headache * 1	39/279 (13.98%)	25/277 (9.03%)	7/71 (9.86%)	4/65 (6.15%)
Dysgeusia * 1	18/279 (6.45%)	9/277 (3.25%)	0/71 (0.00%)	0/65 (0.00%)
Dizziness * 1	22/279 (7.89%)	13/277 (4.69%)	3/71 (4.23%)	4/65 (6.15%)
Psychiatric disorders
Insomnia * 1	31/279 (11.11%)	21/277 (7.58%)	6/71 (8.45%)	5/65 (7.69%)
Renal and urinary disorders
Proteinuria * 1	0/279 (0.00%)	0/277 (0.00%)	9/71 (12.68%)	7/65 (10.77%)
Haematuria * 1	0/279 (0.00%)	0/277 (0.00%)	8/71 (11.27%)	5/65 (7.69%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	60/279 (21.51%)	50/277 (18.05%)	14/71 (19.72%)	11/65 (16.92%)
Dyspnoea * 1	42/279 (15.05%)	22/277 (7.94%)	10/71 (14.08%)	5/65 (7.69%)
Epistaxis * 1	21/279 (7.53%)	14/277 (5.05%)	0/71 (0.00%)	0/65 (0.00%)
Haemoptysis * 1	7/279 (2.51%)	16/277 (5.78%)	0/71 (0.00%)	0/65 (0.00%)
Pleural effusion * 1	0/279 (0.00%)	0/277 (0.00%)	6/71 (8.45%)	2/65 (3.08%)
Productive cough * 1	0/279 (0.00%)	0/277 (0.00%)	5/71 (7.04%)	2/65 (3.08%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform * 1	73/279 (26.16%)	136/277 (49.10%)	14/71 (19.72%)	9/65 (13.85%)
Dry skin * 1	92/279 (32.97%)	92/277 (33.21%)	4/71 (5.63%)	8/65 (12.31%)
Pruritus * 1	50/279 (17.92%)	44/277 (15.88%)	5/71 (7.04%)	4/65 (6.15%)
Alopecia * 1	22/279 (7.89%)	35/277 (12.64%)	1/71 (1.41%)	5/65 (7.69%)
Skin fissures * 1	18/279 (6.45%)	16/277 (5.78%)	0/71 (0.00%)	0/65 (0.00%)
Rash * 1	17/279 (6.09%)	14/277 (5.05%)	0/71 (0.00%)	0/65 (0.00%)
Rash macular * 1	15/279 (5.38%)	12/277 (4.33%)	0/71 (0.00%)	0/65 (0.00%)
Rash papular * 1	18/279 (6.45%)	10/277 (3.61%)	4/71 (5.63%)	3/65 (4.62%)
Palmar-plantar erythrodysaesthesia syndrome * 1	0/279 (0.00%)	0/277 (0.00%)	5/71 (7.04%)	3/65 (4.62%)
Rash maculo-papular * 1	38/279 (13.62%)	46/277 (16.61%)	10/71 (14.08%)	12/65 (18.46%)
Vascular disorders
Hypertension * 1	15/279 (5.38%)	10/277 (3.61%)	4/71 (5.63%)	5/65 (7.69%)
1 Term from vocabulary, 20.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

There were 19 Chinese participants who were included in both the global and China cohort which gives a total of 692 participants instead of a total of 673 participants.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

 

Results Point of Contact

• Name/Title: Global Clinical Leader
• Organization: AstraZeneca AB
• Phone: +46 766 346712
• EMail: ClinicalTrialTransparency@astrazeneca.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Walding A, Skaltsa K, Casamayor M, Ryden A. Time to deterioration of patient-reported outcomes in non-small cell lung cancer: exploring different definitions. Qual Life Res. 2022 Aug;31(8):2535-2543. doi: 10.1007/s11136-022-03088-0. Epub 2022 Jan 31. Erratum In: Qual Life Res. 2022 Mar 24;:

Cheng Y, He Y, Li W, Zhang HL, Zhou Q, Wang B, Liu C, Walding A, Saggese M, Huang X, Fan M, Wang J, Ramalingam SS. Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. Target Oncol. 2021 Mar;16(2):165-176. doi: 10.1007/s11523-021-00794-6. Epub 2021 Feb 5.

Leighl NB, Karaseva N, Nakagawa K, Cho BC, Gray JE, Hovey T, Walding A, Ryden A, Novello S. Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer. Eur J Cancer. 2020 Jan;125:49-57. doi: 10.1016/j.ejca.2019.11.006. Epub 2019 Dec 12.

Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. doi: 10.1056/NEJMoa1913662. Epub 2019 Nov 21.

Brown H, Vansteenkiste J, Nakagawa K, Cobo M, John T, Barker C, Kohlmann A, Todd A, Saggese M, Chmielecki J, Markovets A, Scott M, Ramalingam SS. Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA. J Thorac Oncol. 2020 Jan;15(1):138-143. doi: 10.1016/j.jtho.2019.09.009. Epub 2019 Oct 9.

Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, Pang YK, Cobo M, Kasahara K, Cheng Y, Nogami N, Cho EK, Su WC, Zhang G, Huang X, Li-Sucholeiki X, Lentrichia B, Dearden S, Jenkins S, Saggese M, Rukazenkov Y, Ramalingam SS. Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Nov 15;25(22):6644-6652. doi: 10.1158/1078-0432.CCR-19-1126. Epub 2019 Aug 22.

Planchard D, Boyer MJ, Lee JS, Dechaphunkul A, Cheema PK, Takahashi T, Gray JE, Tiseo M, Ramalingam SS, Todd A, McKeown A, Rukazenkov Y, Ohe Y. Postprogression Outcomes for Osimertinib versus Standard-of-Care EGFR-TKI in Patients with Previously Untreated EGFR-mutated Advanced Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 1;25(7):2058-2063. doi: 10.1158/1078-0432.CCR-18-3325. Epub 2019 Jan 18.

Ohe Y, Imamura F, Nogami N, Okamoto I, Kurata T, Kato T, Sugawara S, Ramalingam SS, Uchida H, Hodge R, Vowler SL, Walding A, Nakagawa K. Osimertinib versus standard-of-care EGFR-TKI as first-line treatment for EGFRm advanced NSCLC: FLAURA Japanese subset. Jpn J Clin Oncol. 2019 Jan 1;49(1):29-36. doi: 10.1093/jjco/hyy179.

Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02296125
• Other Study ID Numbers: D5160C00007; 2014-002694-11 ( EudraCT Number ); U1111-1160-2242 ( Other Grant/Funding Number: 112455 )
• First Submitted: October 22, 2014
• First Posted: November 20, 2014
• Results First Submitted: June 13, 2018
• Results First Posted: November 6, 2018
• Last Update Posted: March 27, 2023