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

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ClinicalTrials.gov Identifier: NCT02296125
Recruitment Status : Active, not recruiting
First Posted : November 20, 2014
Results First Posted : November 6, 2018
Last Update Posted : January 24, 2019
Sponsor:
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
Recruitment Details A total of 556 participants in Global cohort (out of 674 participants in Global and China cohorts) were randomized to treatment at 132 study centres in 29 countries. An additional 17 centres in China enrolled participants 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 SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Period Title: Overall Study
Started 279 277 [1]
Completed [2] 141 64
Not Completed 138 213
Reason Not Completed
Withdrawal by Subject             12             8
Adverse Event             36             50
Severe non-compliance to protocol             0             1
Condition under investigation worsened             87             151
Any reason not specifically recorded             3             3
[1]
183 participant received gefitinib and 93 participants received erlotinib.
[2]
Participants ongoing study treatment at data cut-off
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI Total
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD. Total of all reporting groups
Overall Number of Baseline Participants 279 277 556
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 279 participants 277 participants 556 participants
62.7  (10.70) 63.3  (10.90) 63.0  (10.79)
[1]
Measure Analysis Population Description: The full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
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%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
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%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 279 participants 277 participants 556 participants
Asian (other than Chinese and Japanese) 77 94 171
Chinese 32 24 56
Japanese 65 55 120
Other 103 104 207
Missing 2 0 2
Hispanic or Latino 0 0 2
Smoking status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 279 participants 277 participants 556 participants
Never smoked
182
  65.2%
175
  63.2%
357
  64.2%
Current smokers
8
   2.9%
9
   3.2%
17
   3.1%
Former smokers
89
  31.9%
93
  33.6%
182
  32.7%
1.Primary Outcome
Title Median Progression Free Survival (PFS) (Months)
Hide 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 (approximately 11.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Median (95% Confidence Interval)
Unit of Measure: Months
18.9
(15.2 to 21.4)
10.2
(9.6 to 11.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Osimertinib 80 mg, SoC EGFR-TKI
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]
2.Primary Outcome
Title Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months
Hide 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 (approximately 11.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Median (95% Confidence Interval)
Unit of Measure: Percentage of participants
Progression free at 6 months (%) (95% CI)
88.4
(83.9 to 91.7)
75.2
(69.5 to 79.9)
Progression free at 12 months (%) (95% CI)
68.2
(62.3 to 73.5)
42.3
(36.3 to 48.2)
Progression free at 18 months (%) (95% CI)
50.9
(44.5 to 57.0)
24.4
(19.2 to 30.0)
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as the number (%) of patients 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
Time Frame At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression (approximately 11.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Osimertinib 80 mg, SoC EGFR-TKI
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]
4.Secondary Outcome
Title Duration of Response (DoR)
Hide 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 (approximately 11.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Median (95% Confidence Interval)
Unit of Measure: Months
17.2
(13.8 to 22.0)
8.5
(7.3 to 9.8)
5.Secondary Outcome
Title Disease Control Rate (DCR)
Hide 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 (approximately 11.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Osimertinib 80 mg, SoC EGFR-TKI
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
6.Secondary Outcome
Title Depth of Response
Hide 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 (approximately 11.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Mean (Standard Deviation)
Unit of Measure: Millimeter (mm)
-52.36  (25.065) -45.66  (28.270)
7.Secondary Outcome
Title Overall Survival (OS)- Number of Participants With an Event
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Measure Type: Count of Participants
Unit of Measure: Participants
Death
58
  20.8%
83
  30.0%
Still in survival follow-up
208
  74.6%
177
  63.9%
Terminated prior to death
13
   4.7%
17
   6.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Osimertinib 80 mg, SoC EGFR-TKI
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0068
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.45 to 0.88
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Plasma Concentrations of AZD9291
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Randomized participants received Osimertinib 80 mg orally once daily (QD)
Overall Number of Participants Analyzed 279
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nano moles
Cycle 1 Day 1-Predose Number Analyzed 199 participants
NA [1] 
(NA%)
Cycle 1 Day 1-0.5 - 2 hours Number Analyzed 203 participants
4.9487
(1173.3679%)
Cycle 1 Day 1-3 - 5 hours Number Analyzed 211 participants
129.3340
(171.2983%)
Cycle 3 Day 1- Predose Number Analyzed 183 participants
394.3489
(43.9296%)
Cycle 3 Day 1, 0.5 - 2 hours Number Analyzed 183 participants
397.7406
(45.8548%)
Cycle 3 Day 1, 3 - 5 hours Number Analyzed 182 participants
512.4012
(44.0653%)
Cycle 5 Day 1, Predose Number Analyzed 180 participants
358.5487
(53.8212%)
Cycle 5 Day 1, 0.5 - 2 hours Number Analyzed 177 participants
369.0696
(51.3284%)
Cycle 5 Day 1, 3-5 hours Number Analyzed 179 participants
485.8142
(47.2759%)
Cycle 7 Day 1-Predose Number Analyzed 181 participants
347.6176
(47.7442%)
Cycle 7 Day 1-0.5 - 2 hours Number Analyzed 179 participants
357.8529
(45.0713%)
Cycle 7 Day 1-3-5 hours Number Analyzed 179 participants
475.6587
(41.5778%)
Cycle 9 Day 1-Predose Number Analyzed 165 participants
359.5284
(47.0592%)
Cycle 9 Day 1-0.5-2 hours Number Analyzed 165 participants
363.0106
(48.3837%)
Cycle 9 Day 1-3-5 hours Number Analyzed 163 participants
485.6006
(46.6459%)
Cycle 11 Day 1-Predose Number Analyzed 158 participants
354.5330
(44.4308%)
Cycle 11 Day 1-0.5 -2 hours Number Analyzed 160 participants
367.7450
(45.2003%)
Cycle 11 Day 1-3-5 hours Number Analyzed 161 participants
476.4472
(44.4457%)
Cycle 13 Day 1-Predose Number Analyzed 150 participants
369.9834
(40.1071%)
Cycle 13 Day 1-0.5 -2 hours Number Analyzed 147 participants
371.4157
(42.9794%)
Cycle 13 Day 1-3-5 hours Number Analyzed 147 participants
496.6866
(40.8757%)
[1]
NA as values were not calculable and non-quantifiable
9.Secondary Outcome
Title Plasma Concentrations of Metabolites AZ5104
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Randomized participants received Osimertinib 80 mg orally once daily (QD)
Overall Number of Participants Analyzed 279
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nano moles
Cycle 1 Day 1 Predose Number Analyzed 207 participants
NA [1] 
(NA%)
Cycle 1 Day 1-0.5 - 2 hours Number Analyzed 207 participants
0.1542
(230.5161%)
Cycle 1 Day 1-3 - 5 hours Number Analyzed 223 participants
3.9399
(153.7651%)
Cycle 3 Day 1-Predose Number Analyzed 183 participants
42.9123
(50.2410%)
Cycle 3 Day 1, 0.5 - 2 hours Number Analyzed 183 participants
42.7434
(52.8557%)
Cycle 3 Day 1, 3 - 5 hours Number Analyzed 182 participants
48.3547
(50.4286%)
Cycle 5 Day 1, Predose Number Analyzed 181 participants
39.3718
(56.6226%)
Cycle 5 Day 1, 0.5 - 2 hours Number Analyzed 178 participants
39.4145
(55.3468%)
Cycle 5 Day 1, 3-5 hours Number Analyzed 180 participants
45.6842
(54.3876%)
Cycle 7 Day 1- Predose Number Analyzed 181 participants
38.3847
(50.0861%)
Cycle 7 Day 1, 0.5-2 hours Number Analyzed 179 participants
38.5301
(49.6296%)
Cycle 7 Day 1, 3-5 hours Number Analyzed 179 participants
44.4670
(48.4730%)
Cycle 9 Day 1, Predose Number Analyzed 165 participants
40.1230
(47.0682%)
Cycle 9 Day 1, 0.5-2 hours Number Analyzed 165 participants
40.4987
(47.6483%)
Cycle 9 Day 1, 3-5 hours Number Analyzed 163 participants
46.0310
(44.6875%)
Cycle 11 Day 1, Predose Number Analyzed 158 participants
38.3859
(48.5351%)
Cycle 11 Day 1, 0.5-2 hours Number Analyzed 160 participants
38.7620
(48.1414%)
Cycle 11 Day 1, 3-5 hours Number Analyzed 161 participants
43.9135
(50.6779%)
Cycle 13 Day 1, Predose Number Analyzed 150 participants
40.4356
(47.2671%)
Cycle 13 Day 1, 0.5- 2 hours Number Analyzed 147 participants
40.1116
(46.3929%)
Cycle 13 Day 1, 3-5 hours Number Analyzed 147 participants
45.9083
(44.8309%)
[1]
NA as the values were non-quantifiable and not calculable
10.Secondary Outcome
Title Plasma Concentrations of Metabolite AZ7550
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Randomized participants received Osimertinib 80 mg orally once daily (QD)
Overall Number of Participants Analyzed 279
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nano moles
Cycle 1 Day 1, Predose Number Analyzed 207 participants
NA [1] 
(NA%)
Cycle 1 Day 1, 0.5 - 2 hours Number Analyzed 207 participants
0.1437
(168.2087%)
Cycle 1 Day 1, 3 - 5 hours Number Analyzed 219 participants
1.8610
(147.4624%)
Cycle 3 Day 1, Predose Number Analyzed 183 participants
46.1286
(45.1082%)
Cycle 3 Day 1, 0.5 - 2 hours Number Analyzed 183 participants
46.0045
(45.9584%)
Cycle 3 Day 1, 3 - 5 hours Number Analyzed 182 participants
51.7182
(45.3240%)
Cycle 5 Day 1, Predose Number Analyzed 181 participants
44.4537
(54.9882%)
Cycle 5 Day 1, 0.5 - 2 hours Number Analyzed 178 participants
45.2186
(51.6418%)
Cycle 5 Day 1, 3-5 hours Number Analyzed 180 participants
51.4018
(51.3627%)
Cycle 7 Day 1, Predose Number Analyzed 181 participants
46.2912
(49.8713%)
Cycle 7 Day 1, 0.5-2 hours Number Analyzed 179 participants
46.3540
(49.0845%)
Cycle 7 Day 1,3-5 hours Number Analyzed 179 participants
52.3533
(47.6489%)
Cycle 9 Day 1, Predose Number Analyzed 165 participants
49.6058
(45.5050%)
Cycle 9 Day 1, 0.5-2 hours Number Analyzed 165 participants
49.9381
(46.4568%)
Cycle 9 Day 1, 3-5 hours Number Analyzed 163 participants
56.5354
(45.6736%)
Cycle 11 Day 1, Predose Number Analyzed 158 participants
50.9710
(46.8840%)
Cycle 11 Day 1, 0.5- 2 hours Number Analyzed 160 participants
51.9773
(45.3186%)
Cycle 11 Day 1, 3- 5 hours Number Analyzed 161 participants
57.6986
(48.2382%)
Cycle 13 Day 1, Predose Number Analyzed 150 participants
54.5238
(43.8481%)
Cycle 13 Day 1, 0.5-2 hours Number Analyzed 146 participants
54.1224
(43.7869%)
Cycle 13 Day 1, 3-5 hours Number Analyzed 146 participants
61.6053
(42.2947%)
[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)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Mean (Standard Deviation)
Unit of Measure: Unit on scale
Expectations with Therapy, Week 3 Number Analyzed 227 participants 216 participants
74.1  (22.42) 70.3  (21.85)
Expectations with Therapy, Week 6 Number Analyzed 222 participants 210 participants
76.3  (20.58) 74.0  (19.46)
Feelings about Side-Effects, Week 3 Number Analyzed 227 participants 216 participants
74.5  (17.22) 69.1  (20.96)
Feelings about Side-Effects, Week 6 Number Analyzed 222 participants 210 participants
74.6  (19.83) 69.9  (20.73)
Satisfaction with Therapy, Week 3 Number Analyzed 227 participants 216 participants
84.4  (12.88) 82.6  (13.60)
Satisfaction with Therapy, Week 6 Number Analyzed 222 participants 210 participants
84.2  (13.94) 84.6  (12.38)
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)
Hide 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 [pain in chest, pain in arm or shoulder, and pain in other parts); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. Except for a multi-item scale for dyspnoea, all were single items. 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 better function. Higher scores on the symptoms scales indicated greater symptom burden. The results of the analyses were presented in terms of a least squares mean together with its associated 95% profile likelihood CI.
Time Frame Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
Dyspnoea, First 9 months Number Analyzed 248 participants 252 participants
-4.04
(-5.63 to -2.45)
-4.14
(-5.73 to -2.54)
Dyspnoea, week 1 Number Analyzed 241 participants 246 participants
-3.46
(-5.12 to -1.81)
-3.60
(-5.24 to -1.96)
Dyspnoea, week 2 Number Analyzed 236 participants 236 participants
-3.94
(-5.87 to -2.00)
-3.64
(-5.57 to -1.70)
Dyspnoea, week 3 Number Analyzed 239 participants 237 participants
-3.99
(-5.85 to -2.12)
-3.27
(-5.14 to -1.41)
Dyspnoea, week 4 Number Analyzed 206 participants 211 participants
-4.81
(-6.59 to -3.02)
-4.11
(-5.88 to -2.34)
Dyspnoea, week 5 Number Analyzed 199 participants 196 participants
-3.51
(-5.53 to -1.50)
-5.19
(-7.22 to -3.17)
Dyspnoea, week 6 Number Analyzed 222 participants 214 participants
-4.51
(-6.47 to -2.56)
-4.45
(-6.42 to -2.48)
Dyspnoea, week 12 Number Analyzed 225 participants 203 participants
-3.83
(-5.99 to -1.68)
-5.75
(-7.96 to -3.54)
Dyspnoea, week 18 Number Analyzed 214 participants 199 participants
-4.97
(-7.18 to -2.76)
-5.21
(-7.46 to -2.95)
Dyspnoea, week 24 Number Analyzed 202 participants 185 participants
-4.65
(-7.06 to -2.25)
-4.56
(-7.02 to -2.09)
Dyspnoea, week 30 Number Analyzed 195 participants 172 participants
-3.89
(-6.34 to -1.45)
-3.68
(-6.22 to -1.15)
Dyspnoea, week 36 Number Analyzed 184 participants 151 participants
-2.88
(-5.52 to -0.24)
-2.04
(-4.83 to 0.75)
Cough, First 9 months Number Analyzed 248 participants 252 participants
-10.97
(-12.77 to -9.17)
-11.65
(-13.47 to -9.84)
Cough, week 1 Number Analyzed 241 participants 246 participants
-6.90
(-9.30 to -4.51)
-4.83
(-7.20 to -2.46)
Cough, week 2 Number Analyzed 236 participants 236 participants
-9.04
(-11.58 to -6.49)
-9.52
(-12.05 to -6.98)
Cough, week 3 Number Analyzed 239 participants 237 participants
-9.78
(-12.37 to -7.20)
-10.24
(-12.82 to -7.65)
Cough, week 4 Number Analyzed 206 participants 211 participants
-11.25
(-13.87 to -8.63)
-13.36
(-15.96 to -10.76)
Cough, week 5 Number Analyzed 199 participants 196 participants
-12.98
(-15.64 to -10.31)
-13.55
(-16.21 to -10.88)
Cough, week 6 Number Analyzed 222 participants 214 participants
-11.88
(-14.56 to -9.19)
-11.92
(-14.63 to -9.21)
Cough, week 12 Number Analyzed 225 participants 203 participants
-13.36
(-15.95 to -10.78)
-13.57
(-16.24 to -10.90)
Cough, week 18 Number Analyzed 214 participants 199 participants
-12.31
(-15.25 to -9.37)
-11.00
(-14.03 to -7.98)
Cough, week 24 Number Analyzed 202 participants 185 participants
-11.34
(-14.24 to -8.43)
-13.16
(-16.17 to -10.14)
Cough, week 30 Number Analyzed 195 participants 172 participants
-10.34
(-13.21 to -7.46)
-12.43
(-15.44 to -9.41)
Cough, week 36 Number Analyzed 184 participants 151 participants
-11.49
(-14.48 to -8.49)
-14.62
(-17.85 to -11.39)
Pain in Chest, First 9 months Number Analyzed 248 participants 252 participants
-6.62
(-8.24 to -5.01)
-6.41
(-8.04 to -4.78)
Pain in Chest, week 1 Number Analyzed 241 participants 246 participants
-1.93
(-4.19 to 0.32)
-4.26
(-6.50 to -2.03)
Pain in Chest, week 2 Number Analyzed 236 participants 236 participants
-5.94
(-8.13 to -3.74)
-6.32
(-8.51 to -4.13)
Pain in Chest, week 3 Number Analyzed 239 participants 237 participants
-7.17
(-9.31 to -5.04)
-5.36
(-7.49 to -3.23)
Pain in Chest, week 4 Number Analyzed 206 participants 211 participants
-7.45
(-9.60 to -5.29)
-6.40
(-8.54 to -4.26)
Pain in Chest, week 5 Number Analyzed 199 participants 196 participants
-7.33
(-9.54 to -5.11)
-6.98
(-9.20 to -4.76)
Pain in Chest, week 6 Number Analyzed 222 participants 214 participants
-4.99
(-7.30 to -2.68)
-7.08
(-9.41 to -4.75)
Pain in Chest, week 12 Number Analyzed 225 participants 203 participants
-7.28
(-9.56 to -5.01)
-6.70
(-9.05 to -4.35)
Pain in Chest, week 18 Number Analyzed 214 participants 199 participants
-6.79
(-9.22 to -4.36)
-7.90
(-10.40 to -5.41)
Pain in Chest, week 24 Number Analyzed 202 participants 185 participants
-7.72
(-10.26 to -5.18)
-7.34
(-9.95 to -4.72)
Pain in Chest, week 30 Number Analyzed 195 participants 172 participants
-8.33
(-10.80 to -5.87)
-6.60
(-9.18 to -4.02)
Pain in Chest, week 36 Number Analyzed 184 participants 151 participants
-7.94
(-10.59 to -5.30)
-5.58
(-8.43 to -2.73)
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)
Hide Description The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, which were combined to produce 5 functional scales (Physical, Role, Cognitive, Emotional, Social); 3 symptom scales (Fatigue, Pain, Nausea/Vomiting); 6 individual items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties); 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 results of the analyses were presented in terms of a least squares mean together with its associated 95% profile likelihood CI.
Time Frame Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participant recruited in China, after global recruitment ended, was not included in the FAS.
Arm/Group Title Osimertinib 80 mg SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
Overall Number of Participants Analyzed 279 277
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
Fatigue, First 9 months Number Analyzed 252 participants 247 participants
-5.48
(-7.45 to -3.52)
-4.72
(-6.74 to -2.69)
Fatigue, week 6 Number Analyzed 239 participants 236 participants
-4.13
(-6.35 to -1.91)
-5.78
(-8.02 to -3.54)
Fatigue, week 12 Number Analyzed 237 participants 210 participants
-5.11
(-7.31 to -2.91)
-6.52
(-8.81 to -4.23)
Fatigue, week 18 Number Analyzed 229 participants 214 participants
-6.83
(-9.21 to -4.44)
-5.77
(-8.23 to -3.31)
Fatigue, week 24 Number Analyzed 216 participants 195 participants
-6.18
(-8.75 to -3.61)
-4.96
(-7.63 to -2.28)
Fatigue, week 30 Number Analyzed 207 participants 178 participants
-5.19
(-7.94 to -2.43)
-3.26
(-6.16 to -0.35)
Fatigue, week 36 Number Analyzed 193 participants 158 participants
-5.47
(-8.31 to -2.63)
-2.00
(-2.00 to 1.04)
Appetite Loss, First 9 months Number Analyzed 252 participants 247 participants
-6.15
(-8.39 to -3.90)
-5.64
(-7.96 to -3.32)
Appetite Loss, week 6 Number Analyzed 239 participants 236 participants
-4.54
(-7.36 to -1.72)
-5.67
(-8.52 to -2.83)
Appetite Loss, week 12 Number Analyzed 237 participants 210 participants
-6.52
(-9.43 to -3.62)
-6.95
(-9.98 to -3.91)
Appetite Loss, week 18 Number Analyzed 229 participants 214 participants
-7.27
(-10.09 to -4.45)
-6.84
(-9.75 to -3.92)
Appetite Loss, week 24 Number Analyzed 216 participants 195 participants
-7.14
(-10.27 to -4.01)
-5.08
(-8.35 to -1.81)
Appetite Loss, week 30 Number Analyzed 207 participants 178 participants
-4.50
(-7.74 to -1.26)
-4.17
(-7.60 to -0.74)
Appetite Loss, week 36 Number Analyzed 193 participants 158 participants
-6.90
(-10.00 to -3.81)
-5.15
(-8.49 to -1.81)
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 SoC EGFR-TKI
Hide 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 either gefitinib 250 mg or erlotinib 150 mg orally QD.
All-Cause Mortality
Osimertinib 80 mg SoC EGFR-TKI
Affected / at Risk (%) Affected / at Risk (%)
Total   58/279 (20.79%)   83/277 (29.96%) 
Show Serious Adverse Events Hide Serious Adverse Events
Osimertinib 80 mg SoC EGFR-TKI
Affected / at Risk (%) Affected / at Risk (%)
Total   60/279 (21.51%)   70/277 (25.27%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/279 (0.00%)  1/277 (0.36%) 
Pancytopenia * 1  1/279 (0.36%)  0/277 (0.00%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/279 (0.36%)  0/277 (0.00%) 
Angina pectoris * 1  1/279 (0.36%)  1/277 (0.36%) 
Atrial fibrillation * 1  1/279 (0.36%)  0/277 (0.00%) 
Bundle branch block left * 1  0/279 (0.00%)  1/277 (0.36%) 
Cardiac arrest * 1  1/279 (0.36%)  0/277 (0.00%) 
Cardiac failure chronic * 1  1/279 (0.36%)  0/277 (0.00%) 
Cardiac tamponade * 1  1/279 (0.36%)  0/277 (0.00%) 
Myocardial infarction * 1  1/279 (0.36%)  0/277 (0.00%) 
Tachyarrhythmia * 1  1/279 (0.36%)  0/277 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 1  0/279 (0.00%)  1/277 (0.36%) 
Endocrine disorders     
Inappropriate antidiuretic hormone secretion * 1  1/279 (0.36%)  0/277 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/279 (0.36%)  0/277 (0.00%) 
Chronic gastritis * 1  0/279 (0.00%)  1/277 (0.36%) 
Diarrhoea * 1  2/279 (0.72%)  4/277 (1.44%) 
Enterocolitis * 1  2/279 (0.72%)  0/277 (0.00%) 
Gastritis erosive * 1  1/279 (0.36%)  0/277 (0.00%) 
Gastrointestinal haemorrhage * 1  0/279 (0.00%)  1/277 (0.36%) 
Haemorrhoidal haemorrhage * 1  1/279 (0.36%)  0/277 (0.00%) 
Inguinal hernia * 1  1/279 (0.36%)  0/277 (0.00%) 
Intestinal ischaemia * 1  1/279 (0.36%)  0/277 (0.00%) 
Melaena * 1  0/279 (0.00%)  1/277 (0.36%) 
Mouth ulceration * 1  0/279 (0.00%)  2/277 (0.72%) 
Stomatitis * 1  1/279 (0.36%)  0/277 (0.00%) 
Vomiting * 1  1/279 (0.36%)  5/277 (1.81%) 
General disorders     
Asthenia * 1  2/279 (0.72%)  2/277 (0.72%) 
Chest pain * 1  0/279 (0.00%)  1/277 (0.36%) 
Condition aggravated * 1  0/279 (0.00%)  1/277 (0.36%) 
Death * 1  0/279 (0.00%)  1/277 (0.36%) 
Drug withdrawal syndrome * 1  0/279 (0.00%)  1/277 (0.36%) 
Fatigue * 1  0/279 (0.00%)  1/277 (0.36%) 
General physical health deterioration * 1  0/279 (0.00%)  1/277 (0.36%) 
Pyrexia * 1  2/279 (0.72%)  2/277 (0.72%) 
Hepatobiliary disorders     
Drug-induced liver injury * 1  0/279 (0.00%)  3/277 (1.08%) 
Infections and infestations     
Anal abscess * 1  0/279 (0.00%)  1/277 (0.36%) 
Bacteraemia * 1  0/279 (0.00%)  1/277 (0.36%) 
Clostridial infection * 1  1/279 (0.36%)  0/277 (0.00%) 
Clostridium difficile infection * 1  1/279 (0.36%)  1/277 (0.36%) 
Cystitis * 1  0/279 (0.00%)  1/277 (0.36%) 
Device related infection * 1  0/279 (0.00%)  1/277 (0.36%) 
Diarrhoea infectious * 1  0/279 (0.00%)  1/277 (0.36%) 
Diverticulitis * 1  0/279 (0.00%)  1/277 (0.36%) 
Empyema * 1  1/279 (0.36%)  0/277 (0.00%) 
Endocarditis * 1  0/279 (0.00%)  1/277 (0.36%) 
Enteritis infectious * 1  1/279 (0.36%)  0/277 (0.00%) 
Escherichia urinary tract infection * 1  0/279 (0.00%)  1/277 (0.36%) 
Febrile infection * 1  0/279 (0.00%)  1/277 (0.36%) 
Gastroenteritis * 1  2/279 (0.72%)  1/277 (0.36%) 
Lower respiratory tract infection * 1  1/279 (0.36%)  0/277 (0.00%) 
Lower respiratory tract infection viral * 1  0/279 (0.00%)  1/277 (0.36%) 
Perineal abscess * 1  0/279 (0.00%)  1/277 (0.36%) 
Pharyngotonsillitis * 1  0/279 (0.00%)  1/277 (0.36%) 
Pleural infection * 1  0/279 (0.00%)  1/277 (0.36%) 
Pneumonia * 1  7/279 (2.51%)  7/277 (2.53%) 
Pneumonia mycoplasmal * 1  1/279 (0.36%)  0/277 (0.00%) 
Rectal abscess * 1  0/279 (0.00%)  1/277 (0.36%) 
Respiratory tract infection * 1  1/279 (0.36%)  0/277 (0.00%) 
Salmonella bacteraemia * 1  0/279 (0.00%)  1/277 (0.36%) 
Sepsis * 1  1/279 (0.36%)  3/277 (1.08%) 
Sinusitis * 1  0/279 (0.00%)  1/277 (0.36%) 
Tracheobronchitis * 1  1/279 (0.36%)  0/277 (0.00%) 
Urinary tract infection * 1  1/279 (0.36%)  0/277 (0.00%) 
Bronchitis * 1  0/279 (0.00%)  1/277 (0.36%) 
Injury, poisoning and procedural complications     
Fall * 1  0/279 (0.00%)  1/277 (0.36%) 
Femoral neck fracture * 1  0/279 (0.00%)  1/277 (0.36%) 
Femur fracture * 1  1/279 (0.36%)  0/277 (0.00%) 
Head injury * 1  1/279 (0.36%)  0/277 (0.00%) 
Procedural pneumothorax * 1  0/279 (0.00%)  1/277 (0.36%) 
Subarachnoid haemorrhage * 1  0/279 (0.00%)  1/277 (0.36%) 
Subdural haematoma * 1  1/279 (0.36%)  0/277 (0.00%) 
Wound complication * 1  1/279 (0.36%)  0/277 (0.00%) 
Wrist fracture * 1  1/279 (0.36%)  0/277 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  1/279 (0.36%)  2/277 (0.72%) 
Aspartate aminotransferase increased * 1  1/279 (0.36%)  1/277 (0.36%) 
Electrocardiogram QT prolonged * 1  1/279 (0.36%)  0/277 (0.00%) 
Platelet count decreased * 1  1/279 (0.36%)  1/277 (0.36%) 
Transaminases increased * 1  1/279 (0.36%)  0/277 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/279 (0.72%)  2/277 (0.72%) 
Diabetic ketoacidosis * 1  1/279 (0.36%)  0/277 (0.00%) 
Hyperglycaemia * 1  0/279 (0.00%)  1/277 (0.36%) 
Hypoglycaemia * 1  0/279 (0.00%)  1/277 (0.36%) 
Hyponatraemia * 1  0/279 (0.00%)  1/277 (0.36%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/279 (0.36%)  0/277 (0.00%) 
Flank pain * 1  0/279 (0.00%)  1/277 (0.36%) 
Musculoskeletal chest pain * 1  0/279 (0.00%)  1/277 (0.36%) 
Pathological fracture * 1  0/279 (0.00%)  1/277 (0.36%) 
Rotator cuff syndrome * 1  1/279 (0.36%)  0/277 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Endometrial adenocarcinoma * 1  0/279 (0.00%)  1/277 (0.36%) 
Histiocytic necrotising lymphadenitis * 1  1/279 (0.36%)  0/277 (0.00%) 
Invasive ductal breast carcinoma * 1  1/279 (0.36%)  0/277 (0.00%) 
Ovarian fibroma * 1  0/279 (0.00%)  1/277 (0.36%) 
Prostate cancer * 1  0/279 (0.00%)  1/277 (0.36%) 
Uterine leiomyoma * 1  0/279 (0.00%)  1/277 (0.36%) 
Nervous system disorders     
Brain oedema * 1  0/279 (0.00%)  1/277 (0.36%) 
Cerebral infarction * 1  1/279 (0.36%)  1/277 (0.36%) 
Cerebrovascular accident * 1  0/279 (0.00%)  1/277 (0.36%) 
Cognitive disorder * 1  1/279 (0.36%)  1/277 (0.36%) 
Depressed level of consciousness * 1  1/279 (0.36%)  0/277 (0.00%) 
Dizziness * 1  0/279 (0.00%)  1/277 (0.36%) 
Haemorrhagic stroke * 1  1/279 (0.36%)  0/277 (0.00%) 
Ischaemic stroke * 1  0/279 (0.00%)  1/277 (0.36%) 
Migraine * 1  0/279 (0.00%)  1/277 (0.36%) 
Peripheral motor neuropathy * 1  0/279 (0.00%)  1/277 (0.36%) 
Seizure * 1  0/279 (0.00%)  1/277 (0.36%) 
Spinal cord compression * 1  1/279 (0.36%)  0/277 (0.00%) 
Transient ischaemic attack * 1  1/279 (0.36%)  0/277 (0.00%) 
Psychiatric disorders     
Acute psychosis * 1  1/279 (0.36%)  0/277 (0.00%) 
Confusional state * 1  1/279 (0.36%)  1/277 (0.36%) 
Renal and urinary disorders     
Acute kidney injury * 1  1/279 (0.36%)  0/277 (0.00%) 
Renal failure * 1  1/279 (0.36%)  0/277 (0.00%) 
Ureterolithiasis * 1  0/279 (0.00%)  1/277 (0.36%) 
Reproductive system and breast disorders     
Uterine polyp * 1  0/279 (0.00%)  1/277 (0.36%) 
Respiratory, thoracic and mediastinal disorders     
Asthma * 1  0/279 (0.00%)  1/277 (0.36%) 
Dyspnoea * 1  1/279 (0.36%)  3/277 (1.08%) 
Haemoptysis * 1  0/279 (0.00%)  1/277 (0.36%) 
Hypoxia * 1  1/279 (0.36%)  0/277 (0.00%) 
Interstitial lung disease * 1  4/279 (1.43%)  3/277 (1.08%) 
Pleural effusion * 1  3/279 (1.08%)  3/277 (1.08%) 
Pneumonitis * 1  2/279 (0.72%)  1/277 (0.36%) 
Pneumothorax * 1  0/279 (0.00%)  2/277 (0.72%) 
Pulmonary embolism * 1  4/279 (1.43%)  1/277 (0.36%) 
Pulmonary haemorrhage * 1  0/279 (0.00%)  1/277 (0.36%) 
Respiratory failure * 1  0/279 (0.00%)  2/277 (0.72%) 
Tonsillolith * 1  1/279 (0.36%)  0/277 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis acneiform * 1  0/279 (0.00%)  2/277 (0.72%) 
Toxic epidermal necrolysis * 1  0/279 (0.00%)  1/277 (0.36%) 
Vascular disorders     
Aortic dissection * 1  0/279 (0.00%)  1/277 (0.36%) 
Circulatory collapse * 1  0/279 (0.00%)  1/277 (0.36%) 
Deep vein thrombosis * 1  2/279 (0.72%)  0/277 (0.00%) 
Embolism * 1  1/279 (0.36%)  0/277 (0.00%) 
Orthostatic hypotension * 1  0/279 (0.00%)  1/277 (0.36%) 
Peripheral artery occlusion * 1  0/279 (0.00%)  1/277 (0.36%) 
Thrombophlebitis * 1  1/279 (0.36%)  0/277 (0.00%) 
1
Term from vocabulary, 20.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Osimertinib 80 mg SoC EGFR-TKI
Affected / at Risk (%) Affected / at Risk (%)
Total   273/279 (97.85%)   271/277 (97.83%) 
Blood and lymphatic system disorders     
Anaemia * 1  34/279 (12.19%)  25/277 (9.03%) 
Thrombocytopenia * 1  26/279 (9.32%)  0/277 (0.00%) 
Leukopenia * 1  19/279 (6.81%)  3/277 (1.08%) 
Neutropenia * 1  19/279 (6.81%)  1/277 (0.36%) 
Eye disorders     
Dry eye * 1  21/279 (7.53%)  18/277 (6.50%) 
Gastrointestinal disorders     
Diarrhoea * 1  161/279 (57.71%)  159/277 (57.40%) 
Stomatitis * 1  80/279 (28.67%)  56/277 (20.22%) 
Nausea * 1  39/279 (13.98%)  52/277 (18.77%) 
Constipation * 1  42/279 (15.05%)  35/277 (12.64%) 
Vomiting * 1  31/279 (11.11%)  29/277 (10.47%) 
Dry mouth * 1  12/279 (4.30%)  14/277 (5.05%) 
Abdominal pain * 1  9/279 (3.23%)  15/277 (5.42%) 
General disorders     
Fatigue * 1  38/279 (13.62%)  33/277 (11.91%) 
Pyrexia * 1  28/279 (10.04%)  11/277 (3.97%) 
Oedema peripheral * 1  14/279 (5.02%)  22/277 (7.94%) 
Asthenia * 1  21/279 (7.53%)  10/277 (3.61%) 
Hepatobiliary disorders     
Rash maculo-papular * 1  37/279 (13.26%)  45/277 (16.25%) 
Infections and infestations     
Paronychia * 1  81/279 (29.03%)  80/277 (28.88%) 
Viral upper respiratory tract infection * 1  27/279 (9.68%)  20/277 (7.22%) 
Upper respiratory tract infection * 1  28/279 (10.04%)  18/277 (6.50%) 
Conjunctivitis * 1  14/279 (5.02%)  20/277 (7.22%) 
Pneumonia * 1  18/279 (6.45%)  9/277 (3.25%) 
Investigations     
Aspartate aminotransferase increased * 1  26/279 (9.32%)  68/277 (24.55%) 
Alanine aminotransferase increased * 1  18/279 (6.45%)  75/277 (27.08%) 
Electrocardiogram QT prolonged * 1  28/279 (10.04%)  11/277 (3.97%) 
Weight decreased * 1  14/279 (5.02%)  17/277 (6.14%) 
White blood cell count decreased * 1  24/279 (8.60%)  5/277 (1.81%) 
Blood alkaline phosphatase increased * 1  6/279 (2.15%)  14/277 (5.05%) 
Platelet count decreased * 1  14/279 (5.02%)  5/277 (1.81%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  56/279 (20.07%)  52/277 (18.77%) 
Hypokalaemia * 1  13/279 (4.66%)  17/277 (6.14%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  26/279 (9.32%)  23/277 (8.30%) 
Arthralgia * 1  18/279 (6.45%)  14/277 (5.05%) 
Musculoskeletal pain * 1  20/279 (7.17%)  11/277 (3.97%) 
Myalgia * 1  17/279 (6.09%)  13/277 (4.69%) 
Muscle spasms * 1  16/279 (5.73%)  11/277 (3.97%) 
Pain in extremity * 1  17/279 (6.09%)  4/277 (1.44%) 
Nervous system disorders     
Headache * 1  33/279 (11.83%)  19/277 (6.86%) 
Dysgeusia * 1  18/279 (6.45%)  14/277 (5.05%) 
Dizziness * 1  19/279 (6.81%)  9/277 (3.25%) 
Psychiatric disorders     
Insomnia * 1  26/279 (9.32%)  21/277 (7.58%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  46/279 (16.49%)  42/277 (15.16%) 
Dyspnoea * 1  35/279 (12.54%)  20/277 (7.22%) 
Epistaxis * 1  17/279 (6.09%)  14/277 (5.05%) 
Haemoptysis * 1  7/279 (2.51%)  14/277 (5.05%) 
Skin and subcutaneous tissue disorders     
Dermatitis acneiform * 1  71/279 (25.45%)  134/277 (48.38%) 
Dry skin * 1  88/279 (31.54%)  90/277 (32.49%) 
Pruritus * 1  48/279 (17.20%)  43/277 (15.52%) 
Alopecia * 1  20/279 (7.17%)  35/277 (12.64%) 
Skin fissures * 1  16/279 (5.73%)  14/277 (5.05%) 
Rash * 1  16/279 (5.73%)  11/277 (3.97%) 
Rash macular * 1  14/279 (5.02%)  12/277 (4.33%) 
Rash papular * 1  15/279 (5.38%)  9/277 (3.25%) 
1
Term from vocabulary, 20.0
*
Indicates events were collected by non-systematic assessment
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
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02296125     History of Changes
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: January 24, 2019