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A Study of Erlotinib (Tarceva) After Surgery With or Without Adjuvant Chemotherapy in Non-Small Cell Lung Carcinoma (NSCLC) Patients Who Have Epidermal Growth Factor Receptor (EGFR) Positive Tumors (RADIANT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00373425
Recruitment Status : Completed
First Posted : September 8, 2006
Results First Posted : June 3, 2014
Last Update Posted : September 17, 2015
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( OSI Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Drug: Erlotinib
Drug: Placebo
Enrollment 1252
Recruitment Details Patients with stage IB to IIIA epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) were enrolled globally. 1252 patients were enrolled however 2 patients did not have adequate Health Insurance Portability and Accountability Act (HIPAA) documentation and were removed from the database.
Pre-assignment Details Participants randomized prior to 7 November 2007 comprise the Breached-Protocol Cohort (BPC); those who had not discontinued were offered open-label erlotinib for up to 2 years. Participants randomized subsequently are referred to as the Randomized Cohort.
Arm/Group Title RC: Erlotinib RC: Placebo BPC-NOLC: Erlotinib/Placebo BPC-NOLC: Placebo Only BPC-OLC: Erlotinib
Hide Arm/Group Description Participants in the randomized cohort (RC) who received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity. Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity. The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib. The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib. The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period.
Period Title: Overall Study
Started 623 350 134 11 132
Received Treatment 612 342 134 7 132
Completed 253 [1] 197 [1] 0 [1] 0 [1] 60 [1]
Not Completed 370 153 134 11 72
Reason Not Completed
Relapse of NSCLC             116             104             19             2             26
Adverse Event             191             22             59             0             34
Patient request             35             18             43             6             7
Medical/ethical/noncompliance reason             21             9             10             2             5
Death             7             0             3             1             0
[1]
Completed 2 years of study treatment
Arm/Group Title RC: Erlotinib RC: Placebo BPC-NOLC: Erlotinib/Placebo BPC-NOLC: Placebo Only BPC-OLC: Erlotinib Total
Hide Arm/Group Description Participants in the randomized cohort (RC) who received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity. Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity. The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib. The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib. The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period. Total of all reporting groups
Overall Number of Baseline Participants 623 350 134 11 132 1250
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Randomized Cohort 62.0  (9.28) 61.8  (9.34) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) 61.9  (9.30)
Breached Protocol Cohort, No Open label NA [2]   (NA) NA [2]   (NA) 64.4  (9.33) 62.7  (6.23) NA [2]   (NA) 64.3  (9.13)
Breached Protocol Cohort, Open label NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) 61.8  (9.35) 61.8  (9.35)
[1]
Randomized Cohort only
[2]
Breached Protocol Cohort - No Open Label only
[3]
Breached Protocol Cohort - Open Label only
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Female
257
  41.3%
141
  40.3%
47
  35.1%
2
  18.2%
57
  43.2%
504
  40.3%
Male
366
  58.7%
209
  59.7%
87
  64.9%
9
  81.8%
75
  56.8%
746
  59.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
White 500 279 114 10 111 1014
Black 14 11 4 0 4 33
Asian 107 60 15 1 17 200
American Indian/Alaska Native 1 0 1 0 0 2
Other 1 0 0 0 0 1
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Not Hispanic or Latino 583 322 123 11 124 1163
Hispanic or Latino 40 28 11 0 8 87
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Grade 0 385 211 75 5 77 753
Grade 1 230 134 55 6 54 479
Grade 2 6 5 3 0 1 15
Not measured 2 0 1 0 0 3
[1]
Measure Description: ECOG criteria: 0: Fully active. 1: Ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of all selfcare. 3: Capable of limited selfcare, confined to bed or chair more than 50% of waking hours. 4: Completely disabled, no selfcare, totally confined to bed or chair. 5: Dead.
Cigarette Smoking History  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Never smoked or ≤ 100 cigarettes in lifetime 129 70 19 1 19 238
Former smoker 423 240 103 9 104 879
Current smoker 71 40 12 1 9 133
Histology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Adenocarcinoma 367 211 73 3 76 730
Squamous cell carcinoma 196 111 48 8 49 412
Undifferentiated large cell 22 8 6 0 4 40
Mixed NSCLC 29 18 5 0 1 53
Other 9 2 2 0 2 15
Extent of Disease at Diagnosis   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Stage IA 1 2 1 0 0 4
Stage IB 329 167 64 4 80 644
Stage IIA 42 24 10 1 9 86
Stage IIB 155 99 36 4 23 317
Stage IIIA 93 58 21 1 17 190
Stage IIIB 2 0 2 0 3 7
Stage IV 1 0 0 1 0 2
[1]
Measure Description: Staging is based on the size of the main tumor and whether it has grown into nearby areas, the spread of cancer to nearby lymph nodes and whether the cancer has spread (metastasized) to other organs of the body.
Adjuvant Chemotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Yes 315 200 63 5 68 651
No 308 150 71 6 64 599
Epidermal Growth Factor Receptor (EGFR) Mutation Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Activating mutation-positive 102 59 10 0 16 187
Wild-type 458 245 116 11 107 937
Undetermined 29 16 1 0 1 47
Activating mutation not positive 30 27 5 0 6 68
Not Available 4 3 2 0 2 11
[1]
Measure Description:

EGFR mutation status:

Activating mutation-positive: exon 19 deletion or exon 21 L858R (or both) detected.

Wild-type: neither exon 19 deletion nor exon 21 L858R or any other mutation (exon 18, 19, 20 and 21) detected or undetermined.

Undetermined: exon 19 deletion or exon 21 L858R (or both) mutation status undetermined.

Activating mutation not positive: neither exon 19 deletion nor exon 21 L858R detected or undetermined (includes other mutation positive and other mutation status undetermined).

EGFR Gene Amplification   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 623 participants 350 participants 134 participants 11 participants 132 participants 1250 participants
Positive 445 255 84 8 100 892
Negative 167 87 49 3 32 338
Undetermined 11 8 1 0 0 20
[1]
Measure Description: Analysis of tumor tissue by fluorescent in situ hybridization (FISH), positivity was defined as amplification (EGFR gene to chromosome ratio of ≥ 2 or ≥ 15 EGFR gene copies in ≥ 10% of tumor cells) or high polysomy (≥ 4 EGFR gene copies in ≥ 40% of tumor cells) .
1.Primary Outcome
Title Disease Free Survival (DFS)
Hide Description DFS is the time from the date of randomization until the first day non-small cell lung cancer (NSCLC) relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date.
Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis set (all randomized participants).
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 623 350
Median (95% Confidence Interval)
Unit of Measure: months
50.5 [1] 
(44.7 to NA)
48.2 [1] 
(36.0 to NA)
[1]
Not estimable due to the low number of events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erlotinib, Placebo
Comments The null hypothesis that DFS distributions of the 2 arms were equivalent was tested using an unstratified 2-sided log-rank test at the 0.05 level. The primary analysis of DFS was performed when at least 410 events had accrued. If the result of the primary analysis of DFS was statistically significant favoring the erlotinib treatment arm, the null hypothesis of no treatment difference of key secondary efficacy variables was tested under a hierarchical testing procedure.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3235
Comments If the primary analysis of DFS was not statistically significant, the hierarchical testing procedure would stop and all key secondary efficacy analyses would be nonsignificant; any further analysis of these outcomes would be considered exploratory.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.741 to 1.104
Estimation Comments Hazard ratio: erlotinib to placebo
2.Primary Outcome
Title Disease Free Survival (DFS)
Hide Description DFS is the time from the date of randomization until the first day that non-small cell lung cancer (NSCLC) relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date.
Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cutoff date of 11 June 2014 (maximum time on follow-up was 78 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis set (all randomized participants).
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 623 350
Median (95% Confidence Interval)
Unit of Measure: months
55.0
(47.0 to 64.5)
56.2
(39.7 to 65.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erlotinib, Placebo
Comments The null hypothesis that DFS distributions of the 2 arms were equivalent was tested using an unstratified 2-sided log-rank test at the 0.05 level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5620
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.780 to 1.144
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.
Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis set
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 623 350
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Could not be estimated due to the low number of events
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.
Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis set
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 623 350
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(77.9 to NA)
NA [1] 
(NA to NA)
[1]
Could not be estimated due to the low number of events
5.Secondary Outcome
Title Disease-free Survival in Participants With EGFR Mutation - Positive Tumors
Hide Description Disease-free survival (DFS) is the time from the date of randomization until the first day NSCLC relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.
Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis set participants who are EGFR mutation positive
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 102 59
Median (95% Confidence Interval)
Unit of Measure: months
46.4 [1] 
(39.8 to NA)
28.5 [1] 
(16.7 to NA)
[1]
Could not be estimated due to low number of events
6.Secondary Outcome
Title Disease-free Survival in Participants With EGFR Mutation - Positive Tumors
Hide Description Disease-free survival (DFS) is the time from the date of randomization until the first day NSCLC relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.
Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis set participants who are EGFR mutation positive
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 102 59
Median (95% Confidence Interval)
Unit of Measure: months
47.8
(39.8 to 60.8)
28.5
(16.7 to 61.4)
7.Secondary Outcome
Title Overall Survival in Participants With EGFR Mutation - Positive Tumors
Hide Description

Overall survival is defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.

Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.

Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis participants who were EGFR mutation positive
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 102 59
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(55.4 to NA)
[1]
Could not be estimated due to low number of events
8.Secondary Outcome
Title Overall Survival in Participants With EGFR Mutation - Positive Tumors
Hide Description

Overall survival is defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.

Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.

Time Frame Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized cohort full analysis participants who were EGFR mutation positive
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 102 59
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Could not be estimated due to the low number of events
9.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description

An AE was defined as any untoward medical occurrence in a study participant and did not necessarily have a causal relationship with study treatment.

An AE was considered serious if it resulted in death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a participant, other important medical events, or is on the Astellas Always Serious List.

A drug-related AE was any AE with at least a possible relationship to study treatment as assessed by the investigator. Severity was graded by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v3.0, where Grade 1=Mild AE; Grade=2 Moderate AE; Grade 3=Severe AE; Grade 4=Life-threatening or disabling; Grade 5=Death related to AE. AEs leading to death include deaths that occurred more than 30 days after the last dose of study drug.

Time Frame From the date of first dose of study drug until 30 days after the last dose. The median time on treatment was 11.9 months for erlotinib and 21.9 months for placebo. Data are based off the 11 June 2014 data cut-off date.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Cohort, safety analysis set: all randomized participants who received at least one dose of study drug. One participant in the Randomized Cohort assigned to the erlotinib arm received placebo instead due to a dispensing error and is included in the placebo group for safety analyses.
Arm/Group Title Erlotinib Placebo
Hide Arm/Group Description:
Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed 611 343
Measure Type: Number
Unit of Measure: participants
Any adverse event (AE) 599 307
Grade 3 or higher adverse event 279 96
Serious adverse event (SAE) 118 79
AE leading to discontinuation of study drug 205 29
AE leading to death 14 5
AE leading to dose reduction 150 9
AE leading to dose interruption 114 23
AE leading to dose interruption and reduction 156 5
Drug-related AE 572 181
Drug-related serious AE 15 5
Drug-related AE leading to discontinuation 163 8
Time Frame From the first dose of study drug until 30 days after the last dose. Maximum time on treatment for the Randomized Cohort was 24 months; maximum time on treatment for the BPC was 13 months on blinded study drug and 26 months on open-label erlotinib.
Adverse Event Reporting Description

One participant in the Randomized Cohort assigned to the erlotinib arm received placebo instead due to a dispensing error and is included in the placebo group for safety analyses. For the Breached Protocol Cohort safety analyses are based on the total no open-label and open-label populations.

Safety data are based on the 11 June 2014 cut-off date.

 
Arm/Group Title RC: Erlotinib RC: Placebo BPC-NOLC: Erlotinib/Placebo BPC-NOLC: Placebo Only BPC-OLC: Erlotinib
Hide Arm/Group Description Participants in the randomized cohort (RC) who received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity. Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity. The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib. The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib. The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period.
All-Cause Mortality
RC: Erlotinib RC: Placebo BPC-NOLC: Erlotinib/Placebo BPC-NOLC: Placebo Only BPC-OLC: Erlotinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
RC: Erlotinib RC: Placebo BPC-NOLC: Erlotinib/Placebo BPC-NOLC: Placebo Only BPC-OLC: Erlotinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   118/611 (19.31%)   79/343 (23.03%)   21/134 (15.67%)   1/11 (9.09%)   41/132 (31.06%) 
Blood and lymphatic system disorders           
Anaemia  1  4/611 (0.65%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Lymphadenopathy  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Haemolytic anaemia  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cardiac disorders           
Myocardial infarction  1  3/611 (0.49%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pericarditis  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Acute myocardial infarction  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Atrial fibrillation  1  1/611 (0.16%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  1/132 (0.76%) 
Cardiac failure  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cardio-respiratory arrest  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pericardial effusion  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Acute coronary syndrome  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Angina pectoris  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Angina unstable  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Arrhythmia  1  0/611 (0.00%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  1/132 (0.76%) 
Ischaemic cardiomyopathy  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Coronary artery disease  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  1/132 (0.76%) 
Cardiac failure congestive  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Congenital, familial and genetic disorders           
Rathke's cleft cyst  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Atrial septal defect  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Ear and labyrinth disorders           
Deafness  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Deafness neurosensory  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Endocrine disorders           
Thyroid cyst  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Eye disorders           
Cataract  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Blindness  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Retinal haemorrhage  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Gastrointestinal disorders           
Diarrhoea  1  4/611 (0.65%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  1/132 (0.76%) 
Duodenal ulcer  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Gastrointestinal haemorrhage  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Abdominal pain  1  1/611 (0.16%)  3/343 (0.87%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Dysphagia  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Gastric ulcer  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Gingival bleeding  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Haematemesis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Ileus  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Intestinal obstruction  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Oesophagitis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Small intestinal obstruction  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Subileus  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Volvulus  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Colitis ischaemic  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Enterovesical fistula  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Gastrooesophageal reflux disease  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Nausea  1  0/611 (0.00%)  1/343 (0.29%)  2/134 (1.49%)  0/11 (0.00%)  1/132 (0.76%) 
Pancreatitis  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Rectal haemorrhage  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Vomiting  1  0/611 (0.00%)  1/343 (0.29%)  2/134 (1.49%)  0/11 (0.00%)  1/132 (0.76%) 
Diarrhoea haemorrhagic  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Peptic ulcer perforation  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Peritonitis  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Enteritis  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Gastric dysplasia  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Haemorrhoids  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Tooth resorption  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Upper gastrointestinal haemorrhage  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
General disorders           
Asthenia  1  3/611 (0.49%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Fatigue  1  2/611 (0.33%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Chest pain  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Death  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
General physical health deterioration  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Multi-organ failure  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pyrexia  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pain  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Performance status decreased  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Sudden death  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Hepatobiliary disorders           
Cholecystitis acute  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cholangitis acute  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cholecystitis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Jaundice  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Immune system disorders           
Anaphylactic shock  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Infections and infestations           
Pneumonia  1  8/611 (1.31%)  2/343 (0.58%)  2/134 (1.49%)  0/11 (0.00%)  3/132 (2.27%) 
Respiratory tract infection  1  4/611 (0.65%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Bronchitis  1  2/611 (0.33%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Sepsis  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Urinary tract infection  1  2/611 (0.33%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Appendicitis  1  1/611 (0.16%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Bronchopneumonia  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cellulitis  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Clostridial infection  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Dermatitis infected  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Diverticulitis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Eczema infected  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Empyema  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Haematoma infection  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Osteomyelitis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pertussis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pyelonephritis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Upper respiratory tract infection  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Bronchitis acute  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Clostridium difficile colitis  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Herpes zoster  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Lobar pneumonia  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Lung infection  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Meningitis viral  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pulmonary tuberculosis  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Wound infection staphylococcal  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Device related infection  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Arthritis infective  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Bacterial infection  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Nasal abscess  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Nasopharyngitis  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pneumonia bacterial  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Injury, poisoning and procedural complications           
Fall  1  3/611 (0.49%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Clavicle fracture  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Haemothorax  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Injury  1  1/611 (0.16%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Laceration  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Polytraumatism  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Post procedural haematoma  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Procedural pain  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Rib fracture  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Spinal compression fracture  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Ankle fracture  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Bronchial anastomosis complication  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Concussion  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Femur fracture  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Road traffic accident  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pelvic fracture  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  1/132 (0.76%) 
Suture rupture  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Hip fracture  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Incisional hernia  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Postoperative fever  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Investigations           
Blood bilirubin increased  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Weight decreased  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Blood creatinine increased  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  3/611 (0.49%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Anorexia  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Fluid retention  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Hypokalaemia  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Hyponatraemia  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Oral intake reduced  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Hypercalcaemia  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Musculoskeletal and connective tissue disorders           
Intervertebral disc protrusion  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Back pain  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Bone pain  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Flank pain  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Muscular weakness  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pain in extremity  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Spinal column stenosis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Arthralgia  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Muscle haemorrhage  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Musculoskeletal chest pain  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Musculoskeletal pain  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Rotator cuff syndrome  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Osteoarthritis  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Spondylolisthesis  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Malignant neoplasm progression  1  4/611 (0.65%)  3/343 (0.87%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Laryngeal cancer  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Lung squamous cell carcinoma stage unspecified  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Metastases to central nervous system  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Neurilemmoma  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Prostate cancer  1  3/611 (0.49%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  3/132 (2.27%) 
Throat cancer  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cancer pain  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Chronic myeloid leukaemia  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Colon cancer  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Renal cell carcinoma stage unspecified  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Sarcoma  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Colon adenoma  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Lung neoplasm  1  5/611 (0.82%)  3/343 (0.87%)  0/134 (0.00%)  0/11 (0.00%)  2/132 (1.52%) 
Small cell lung cancer stage unspecified  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  2/132 (1.52%) 
Basal cell carcinoma  1  1/611 (0.16%)  5/343 (1.46%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Bladder cancer  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Conjunctival neoplasm  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Malignant ascites  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Malignant melanoma  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Prostate cancer stage I  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Squamous cell carcinoma  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Squamous cell carcinoma of skin  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Thyroid cancer  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Thyroid neoplasm  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Tonsil cancer  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Uterine cancer  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Nervous system disorders           
Cerebrovascular accident  1  3/611 (0.49%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Hemiparesis  1  3/611 (0.49%)  4/343 (1.17%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Headache  1  2/611 (0.33%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  1/132 (0.76%) 
Loss of consciousness  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cerebral infarction  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cerebral ischaemia  1  1/611 (0.16%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Intracranial pressure increased  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Memory impairment  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Monoparesis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Neuropathy peripheral  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Peripheral motor neuropathy  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Presyncope  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Convulsion  1  1/611 (0.16%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Dysphasia  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
IIIrd nerve paralysis  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Peripheral sensory neuropathy  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Syncope  1  0/611 (0.00%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Transient ischaemic attack  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cerebral artery embolism  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Facial paresis  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Normal pressure hydrocephalus  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Sudden onset of sleep  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Balance disorder  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Brain mass  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Dizziness  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Ischaemic stroke  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Neuralgia  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Cerebellar infarction  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Epilepsy  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Psychiatric disorders           
Confusional state  1  1/611 (0.16%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Disorientation  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Mental status changes  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  2/132 (1.52%) 
Inappropriate affect  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Renal and urinary disorders           
Renal failure acute  1  4/611 (0.65%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Nephrolithiasis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Urinary bladder haemorrhage  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Urinary incontinence  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Calculus ureteric  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Urethral obstruction  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Reproductive system and breast disorders           
Uterovaginal prolapse  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Dyspnoea  1  6/611 (0.98%)  5/343 (1.46%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pulmonary embolism  1  3/611 (0.49%)  5/343 (1.46%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pleural effusion  1  2/611 (0.33%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Asthma  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Bronchial hyperreactivity  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Cough  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Epistaxis  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Hypoxia  1  1/611 (0.16%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Lung disorder  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pneumonia aspiration  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pulmonary congestion  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Respiratory failure  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Chronic obstructive pulmonary disease  1  0/611 (0.00%)  3/343 (0.87%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Lower respiratory tract inflammation  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Pneumothorax  1  0/611 (0.00%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pulmonary infarction  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Acute respiratory distress syndrome  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Apnoea  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  1/11 (9.09%)  0/132 (0.00%) 
Interstitial lung disease  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Bronchial fistula  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Hydrothorax  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pneumonitis  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pulmonary granuloma  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pleural fibrosis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Pulmonary fibrosis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Skin and subcutaneous tissue disorders           
Dermatitis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Skin ulcer  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Rash  1  0/611 (0.00%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Vascular disorders           
Cardiovascular insufficiency  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Deep vein thrombosis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Hypotension  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Peripheral arterial occlusive disease  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Temporal arteritis  1  1/611 (0.16%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Aortic aneurysm  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Aortic occlusion  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Hypertension  1  0/611 (0.00%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  1/132 (0.76%) 
Hypertensive crisis  1  0/611 (0.00%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  0/132 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
RC: Erlotinib RC: Placebo BPC-NOLC: Erlotinib/Placebo BPC-NOLC: Placebo Only BPC-OLC: Erlotinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   590/611 (96.56%)   288/343 (83.97%)   125/134 (93.28%)   4/11 (36.36%)   130/132 (98.48%) 
Blood and lymphatic system disorders           
Anaemia  1  16/611 (2.62%)  6/343 (1.75%)  2/134 (1.49%)  0/11 (0.00%)  4/132 (3.03%) 
Ear and labyrinth disorders           
Vertigo  1  6/611 (0.98%)  6/343 (1.75%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Eye disorders           
Conjunctivitis  1  34/611 (5.56%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  5/132 (3.79%) 
Dry eye  1  31/611 (5.07%)  3/343 (0.87%)  6/134 (4.48%)  0/11 (0.00%)  5/132 (3.79%) 
Eye irritation  1  8/611 (1.31%)  3/343 (0.87%)  2/134 (1.49%)  0/11 (0.00%)  4/132 (3.03%) 
Gastrointestinal disorders           
Diarrhoea  1  318/611 (52.05%)  54/343 (15.74%)  54/134 (40.30%)  0/11 (0.00%)  86/132 (65.15%) 
Nausea  1  84/611 (13.75%)  44/343 (12.83%)  17/134 (12.69%)  1/11 (9.09%)  28/132 (21.21%) 
Stomatitis  1  61/611 (9.98%)  4/343 (1.17%)  8/134 (5.97%)  0/11 (0.00%)  15/132 (11.36%) 
Vomiting  1  55/611 (9.00%)  23/343 (6.71%)  10/134 (7.46%)  0/11 (0.00%)  12/132 (9.09%) 
Constipation  1  35/611 (5.73%)  23/343 (6.71%)  7/134 (5.22%)  0/11 (0.00%)  14/132 (10.61%) 
Abdominal pain  1  34/611 (5.56%)  11/343 (3.21%)  6/134 (4.48%)  0/11 (0.00%)  14/132 (10.61%) 
Dyspepsia  1  30/611 (4.91%)  14/343 (4.08%)  4/134 (2.99%)  0/11 (0.00%)  15/132 (11.36%) 
Abdominal pain upper  1  28/611 (4.58%)  20/343 (5.83%)  0/134 (0.00%)  0/11 (0.00%)  11/132 (8.33%) 
Dry mouth  1  21/611 (3.44%)  3/343 (0.87%)  7/134 (5.22%)  0/11 (0.00%)  7/132 (5.30%) 
Gastrooesophageal reflux disease  1  20/611 (3.27%)  8/343 (2.33%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Cheilitis  1  4/611 (0.65%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  8/132 (6.06%) 
Mouth ulceration  1  13/611 (2.13%)  1/343 (0.29%)  1/134 (0.75%)  0/11 (0.00%)  5/132 (3.79%) 
Flatulence  1  11/611 (1.80%)  6/343 (1.75%)  2/134 (1.49%)  0/11 (0.00%)  4/132 (3.03%) 
General disorders           
Fatigue  1  118/611 (19.31%)  49/343 (14.29%)  23/134 (17.16%)  0/11 (0.00%)  34/132 (25.76%) 
Asthenia  1  37/611 (6.06%)  21/343 (6.12%)  6/134 (4.48%)  0/11 (0.00%)  6/132 (4.55%) 
Mucosal inflammation  1  27/611 (4.42%)  2/343 (0.58%)  6/134 (4.48%)  0/11 (0.00%)  12/132 (9.09%) 
Pyrexia  1  23/611 (3.76%)  13/343 (3.79%)  6/134 (4.48%)  1/11 (9.09%)  9/132 (6.82%) 
Xerosis  1  19/611 (3.11%)  5/343 (1.46%)  0/134 (0.00%)  0/11 (0.00%)  1/132 (0.76%) 
Oedema peripheral  1  18/611 (2.95%)  11/343 (3.21%)  1/134 (0.75%)  0/11 (0.00%)  5/132 (3.79%) 
Chest pain  1  15/611 (2.45%)  12/343 (3.50%)  2/134 (1.49%)  0/11 (0.00%)  4/132 (3.03%) 
Non-cardiac chest pain  1  12/611 (1.96%)  9/343 (2.62%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Infections and infestations           
Paronychia  1  39/611 (6.38%)  2/343 (0.58%)  4/134 (2.99%)  0/11 (0.00%)  6/132 (4.55%) 
Upper respiratory tract infection  1  30/611 (4.91%)  15/343 (4.37%)  0/134 (0.00%)  0/11 (0.00%)  13/132 (9.85%) 
Nasopharyngitis  1  29/611 (4.75%)  30/343 (8.75%)  2/134 (1.49%)  0/11 (0.00%)  17/132 (12.88%) 
Bronchitis  1  21/611 (3.44%)  12/343 (3.50%)  1/134 (0.75%)  0/11 (0.00%)  9/132 (6.82%) 
Rash pustular  1  19/611 (3.11%)  1/343 (0.29%)  3/134 (2.24%)  0/11 (0.00%)  13/132 (9.85%) 
Urinary tract infection  1  19/611 (3.11%)  12/343 (3.50%)  1/134 (0.75%)  0/11 (0.00%)  3/132 (2.27%) 
Sinusitis  1  7/611 (1.15%)  8/343 (2.33%)  3/134 (2.24%)  0/11 (0.00%)  7/132 (5.30%) 
Ear infection  1  2/611 (0.33%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  5/132 (3.79%) 
Nail infection  1  2/611 (0.33%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  5/132 (3.79%) 
Rhinitis  1  12/611 (1.96%)  6/343 (1.75%)  1/134 (0.75%)  0/11 (0.00%)  5/132 (3.79%) 
Localised infection  1  4/611 (0.65%)  2/343 (0.58%)  0/134 (0.00%)  0/11 (0.00%)  4/132 (3.03%) 
Pneumonia  1  16/611 (2.62%)  5/343 (1.46%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Skin infection  1  3/611 (0.49%)  0/343 (0.00%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Injury, poisoning and procedural complications           
Procedural pain  1  9/611 (1.47%)  6/343 (1.75%)  4/134 (2.99%)  0/11 (0.00%)  5/132 (3.79%) 
Investigations           
Weight decreased  1  56/611 (9.17%)  19/343 (5.54%)  2/134 (1.49%)  0/11 (0.00%)  19/132 (14.39%) 
Weight increased  1  16/611 (2.62%)  20/343 (5.83%)  1/134 (0.75%)  0/11 (0.00%)  6/132 (4.55%) 
Blood sodium decreased  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  1/11 (9.09%)  0/132 (0.00%) 
Alanine aminotransferase increased  1  7/611 (1.15%)  6/343 (1.75%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Metabolism and nutrition disorders           
Anorexia  1  80/611 (13.09%)  24/343 (7.00%)  20/134 (14.93%)  1/11 (9.09%)  20/132 (15.15%) 
Dehydration  1  5/611 (0.82%)  1/343 (0.29%)  4/134 (2.99%)  0/11 (0.00%)  4/132 (3.03%) 
Musculoskeletal and connective tissue disorders           
Back pain  1  40/611 (6.55%)  24/343 (7.00%)  3/134 (2.24%)  0/11 (0.00%)  12/132 (9.09%) 
Muscle spasms  1  36/611 (5.89%)  7/343 (2.04%)  1/134 (0.75%)  0/11 (0.00%)  10/132 (7.58%) 
Musculoskeletal chest pain  1  28/611 (4.58%)  10/343 (2.92%)  1/134 (0.75%)  0/11 (0.00%)  3/132 (2.27%) 
Arthralgia  1  23/611 (3.76%)  25/343 (7.29%)  4/134 (2.99%)  0/11 (0.00%)  14/132 (10.61%) 
Pain in extremity  1  23/611 (3.76%)  12/343 (3.50%)  3/134 (2.24%)  0/11 (0.00%)  12/132 (9.09%) 
Musculoskeletal pain  1  20/611 (3.27%)  23/343 (6.71%)  2/134 (1.49%)  0/11 (0.00%)  9/132 (6.82%) 
Myalgia  1  18/611 (2.95%)  6/343 (1.75%)  4/134 (2.99%)  0/11 (0.00%)  6/132 (4.55%) 
Nervous system disorders           
Headache  1  42/611 (6.87%)  40/343 (11.66%)  10/134 (7.46%)  0/11 (0.00%)  13/132 (9.85%) 
Dizziness  1  26/611 (4.26%)  22/343 (6.41%)  9/134 (6.72%)  1/11 (9.09%)  13/132 (9.85%) 
Dysgeusia  1  26/611 (4.26%)  4/343 (1.17%)  5/134 (3.73%)  0/11 (0.00%)  13/132 (9.85%) 
Paraesthesia  1  20/611 (3.27%)  15/343 (4.37%)  1/134 (0.75%)  0/11 (0.00%)  0/132 (0.00%) 
Lethargy  1  2/611 (0.33%)  0/343 (0.00%)  0/134 (0.00%)  1/11 (9.09%)  0/132 (0.00%) 
Somnolence  1  4/611 (0.65%)  0/343 (0.00%)  0/134 (0.00%)  1/11 (9.09%)  0/132 (0.00%) 
Neuropathy  1  9/611 (1.47%)  2/343 (0.58%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Peripheral sensory neuropathy  1  9/611 (1.47%)  4/343 (1.17%)  2/134 (1.49%)  0/11 (0.00%)  4/132 (3.03%) 
Psychiatric disorders           
Insomnia  1  40/611 (6.55%)  21/343 (6.12%)  6/134 (4.48%)  0/11 (0.00%)  16/132 (12.12%) 
Depression  1  33/611 (5.40%)  12/343 (3.50%)  5/134 (3.73%)  0/11 (0.00%)  6/132 (4.55%) 
Anxiety  1  20/611 (3.27%)  14/343 (4.08%)  5/134 (3.73%)  0/11 (0.00%)  7/132 (5.30%) 
Aggression  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  1/11 (9.09%)  0/132 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  121/611 (19.80%)  69/343 (20.12%)  17/134 (12.69%)  0/11 (0.00%)  29/132 (21.97%) 
Dyspnoea  1  85/611 (13.91%)  61/343 (17.78%)  15/134 (11.19%)  0/11 (0.00%)  18/132 (13.64%) 
Epistaxis  1  47/611 (7.69%)  4/343 (1.17%)  4/134 (2.99%)  0/11 (0.00%)  11/132 (8.33%) 
Haemoptysis  1  20/611 (3.27%)  4/343 (1.17%)  3/134 (2.24%)  0/11 (0.00%)  4/132 (3.03%) 
Rhinorrhoea  1  19/611 (3.11%)  12/343 (3.50%)  3/134 (2.24%)  0/11 (0.00%)  7/132 (5.30%) 
Productive cough  1  16/611 (2.62%)  14/343 (4.08%)  3/134 (2.24%)  0/11 (0.00%)  6/132 (4.55%) 
Pleural fibrosis  1  0/611 (0.00%)  0/343 (0.00%)  0/134 (0.00%)  1/11 (9.09%)  0/132 (0.00%) 
Nasal ulcer  1  5/611 (0.82%)  0/343 (0.00%)  0/134 (0.00%)  0/11 (0.00%)  5/132 (3.79%) 
Pharyngolaryngeal pain  1  13/611 (2.13%)  8/343 (2.33%)  3/134 (2.24%)  0/11 (0.00%)  5/132 (3.79%) 
Dyspnoea exertional  1  9/611 (1.47%)  9/343 (2.62%)  2/134 (1.49%)  0/11 (0.00%)  4/132 (3.03%) 
Skin and subcutaneous tissue disorders           
Rash  1  356/611 (58.27%)  58/343 (16.91%)  51/134 (38.06%)  0/11 (0.00%)  72/132 (54.55%) 
Pruritus  1  161/611 (26.35%)  51/343 (14.87%)  21/134 (15.67%)  0/11 (0.00%)  29/132 (21.97%) 
Dry skin  1  127/611 (20.79%)  50/343 (14.58%)  15/134 (11.19%)  0/11 (0.00%)  41/132 (31.06%) 
Dermatitis acneiform  1  111/611 (18.17%)  19/343 (5.54%)  37/134 (27.61%)  0/11 (0.00%)  45/132 (34.09%) 
Alopecia  1  67/611 (10.97%)  11/343 (3.21%)  12/134 (8.96%)  0/11 (0.00%)  22/132 (16.67%) 
Rash erythematous  1  30/611 (4.91%)  6/343 (1.75%)  6/134 (4.48%)  0/11 (0.00%)  12/132 (9.09%) 
Rash maculo-papular  1  28/611 (4.58%)  3/343 (0.87%)  4/134 (2.99%)  0/11 (0.00%)  7/132 (5.30%) 
Skin fissures  1  26/611 (4.26%)  2/343 (0.58%)  1/134 (0.75%)  0/11 (0.00%)  9/132 (6.82%) 
Acne  1  25/611 (4.09%)  10/343 (2.92%)  6/134 (4.48%)  0/11 (0.00%)  3/132 (2.27%) 
Rash papular  1  25/611 (4.09%)  5/343 (1.46%)  1/134 (0.75%)  0/11 (0.00%)  7/132 (5.30%) 
Erythema  1  24/611 (3.93%)  5/343 (1.46%)  10/134 (7.46%)  0/11 (0.00%)  13/132 (9.85%) 
Nail disorder  1  23/611 (3.76%)  2/343 (0.58%)  1/134 (0.75%)  0/11 (0.00%)  9/132 (6.82%) 
Skin exfoliation  1  23/611 (3.76%)  4/343 (1.17%)  6/134 (4.48%)  0/11 (0.00%)  8/132 (6.06%) 
Exfoliative rash  1  19/611 (3.11%)  2/343 (0.58%)  2/134 (1.49%)  0/11 (0.00%)  11/132 (8.33%) 
Blister  1  8/611 (1.31%)  0/343 (0.00%)  5/134 (3.73%)  0/11 (0.00%)  1/132 (0.76%) 
Night sweats  1  3/611 (0.49%)  0/343 (0.00%)  4/134 (2.99%)  1/11 (9.09%)  1/132 (0.76%) 
Rash pruritic  1  10/611 (1.64%)  1/343 (0.29%)  1/134 (0.75%)  1/11 (9.09%)  5/132 (3.79%) 
Dermatitis  1  4/611 (0.65%)  1/343 (0.29%)  0/134 (0.00%)  0/11 (0.00%)  4/132 (3.03%) 
Eczema  1  11/611 (1.80%)  5/343 (1.46%)  0/134 (0.00%)  0/11 (0.00%)  4/132 (3.03%) 
Skin lesion  1  15/611 (2.45%)  4/343 (1.17%)  1/134 (0.75%)  0/11 (0.00%)  4/132 (3.03%) 
Rash macular  1  18/611 (2.95%)  7/343 (2.04%)  2/134 (1.49%)  0/11 (0.00%)  8/132 (6.06%) 
Vascular disorders           
Hypertension  1  22/611 (3.60%)  14/343 (4.08%)  2/134 (1.49%)  0/11 (0.00%)  8/132 (6.06%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
Company makes no warranties or representations of any kind as to the currency or completeness of the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose and shall not be liable for any damages.
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.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site’s manuscript at least 60 days prior to publication for review and comment. Sponsor may delay the publication for up to 6 months to seek patent protection.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Medical Director, Medical Oncology
Organization: Astellas Pharma Global Development, Inc.
EMail: clinicaltrial.disclosure@us.astellas.com
Layout table for additonal information
Responsible Party: Astellas Pharma Inc ( OSI Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00373425    
Other Study ID Numbers: OSI-774-302
2005-001747-29 ( EudraCT Number )
First Submitted: September 7, 2006
First Posted: September 8, 2006
Results First Submitted: April 2, 2014
Results First Posted: June 3, 2014
Last Update Posted: September 17, 2015