Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) in Elderly Patients With Advanced Non-Small Cell Lung Cancer (NCT NCT01196078)

NCT ID: NCT01196078

Last Updated: 2015-07-27

Results Overview

CR was defined as disappearance of all target lesions. PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Participants experiencing either a CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) were classified as responders. Participants with tumour assessment unevaluable were viewed as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

114 participants

Primary outcome timeframe

Screening, Day 1 of Cycles 3 and 5 and at End of treatment up to 1 year

Results posted on

2015-07-27

Participant Flow

Participant milestones

Participant milestones
Measure	Erlotinib Participants received erlotinib 150 milligrams (mg), tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine Cycle 1 (21-day cycle): Participants received vinorelbine 60 milligrams per square meter (mg/m\^2) orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 adverse events \[AEs\]) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Study STARTED	57	57
Overall Study COMPLETED	24	20
Overall Study NOT COMPLETED	33	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib Participants received erlotinib 150 milligrams (mg), tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine Cycle 1 (21-day cycle): Participants received vinorelbine 60 milligrams per square meter (mg/m\^2) orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 adverse events \[AEs\]) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Study Withdrawal by Subject	3	5
Overall Study Adverse Event	4	4
Overall Study Protocol Violation	2	1
Overall Study Lack of Efficacy	17	23
Overall Study Lost to Follow-up	1	0
Overall Study Death	6	4

Baseline Characteristics

A Study of Tarceva (Erlotinib) in Elderly Patients With Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=56 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.	Total n=113 Participants Total of all reporting groups
Age, Continuous	78 years STANDARD_DEVIATION 4.98 • n=5 Participants	78 years STANDARD_DEVIATION 5.32 • n=7 Participants	78 years STANDARD_DEVIATION 5.60 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	45 Participants n=7 Participants	92 Participants n=5 Participants

PRIMARY outcome

Timeframe: Screening, Day 1 of Cycles 3 and 5 and at End of treatment up to 1 year

Population: ITT population

Outcome measures

Outcome measures
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=56 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Percentage of Participants Achieving a Best Overall Response of Complete Response (CR) or Partial Response (PR)	22.81 percentage of participants	8.93 percentage of participants

SECONDARY outcome

Timeframe: Screening, Day 1 of Cycles 3 and 5 and at End of treatment up to 1 year

Population: ITT Population

Disease control was defined as achieving a best overall response of CR, PR, or stable disease (SD) according to RECIST criteria. Participants with tumor assessment unevaluable were viewed as uncontrolled.

Outcome measures

Outcome measures
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=56 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Percentage of Participants Achieving Disease Control	71.93 percentage of participants	57.14 percentage of participants

SECONDARY outcome

Timeframe: Screening, Day 1 of Cycles 3 and 5, every 4th cycle during post-study treatment, and every 3 cycles during follow-up

Population: ITT population; only participants with a response (CR or PR) were included in the analysis.

Duration of response was defined similarly for complete and partial responders. Complete response lasted from the date the complete response was first recorded to the date on which progressive disease was first noted or date of death. Partial response lasted from the date of partial response to the date of the first observation of progressive disease or date of death.

Outcome measures

Outcome measures
Measure	Erlotinib n=13 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=5 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Duration of Response Among Participants Who Achieved Either a CR or PR	10.89 months Interval 5.48 to 22.23	8.75 months Interval 2.75 to Upper limit of the 95% CI could not be calculated because the duration of follow-up was too short to observe enough events for complete data estimation.

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 3, and 5 or first documentation of progressive disease or death

Population: ITT population

Progressive disease was defined using RECIST as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=56 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Percentage of Participants With Disease Progression	63.16 percentage of participants	58.93 percentage of participants

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 3, and 5 or first documentation of progressive disease or death

Population: ITT population

Time to disease progression was defined as the interval between the day of randomization and the first documentation of progressive disease or death.

Outcome measures

Outcome measures
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=56 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Time to Disease Progression	6.66 months Interval 4.43 to 9.05	3.87 months Interval 2.49 to 6.92

SECONDARY outcome

Timeframe: Day 1 of Cycles 1 through 6 to date of death or date of last follow-up assessment

Population: ITT population

Overall survival was defined as the time from the date of randomization to the date of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no postbaseline information were censored at the time of randomization. Progressive disease was defined per RECIST as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=56 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Survival: Percentage of Participants With an Progressive Disease or Death	56.14 percentage of participants	48.21 percentage of participants

SECONDARY outcome

Timeframe: Day 1 of Cycles 1 through 6 to date of death or date of last follow-up assessment

Population: ITT population

Overall survival was defined as the time from the date of randomization to the date of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no post baseline information were censored at the time of randomization. Overall median time to event was assessed for the population that experienced an event.

Outcome measures

Outcome measures
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=56 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Survival: Time to Event	11.21 months Interval 6.79 to 19.57	10.36 months Interval 7.67 to Upper limit of the 95% CI could not be calculated because the duration of follow-up was too short to observe enough events for complete data estimation.

SECONDARY outcome

Timeframe: Baseline and Day 1 of Cycles 2, 3, 4, 5, 6 and End of study

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

The FACT Questionnaire contains 4 general and 1 lung cancer symptom-specific subscale, including Physical Well-Being (PWB), Social/family Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and the 8-item Lung Cancer Subscale (LCS) that assess symptoms commonly reported by participants with lung cancer. Each subscale was assessed by a five-point scale from 0 (not at all) to 4 (very much) to determine the quality of life. PWB, SWB and FWB scores ranged from 0-28 and EWB scores ranged from 0-24. LCS scores ranged from 0-36. For subscales of FWB and SWB, questionnaires of EWB, and additional concerns questions, the higher score represented 'Improved'. For other subscales and questionnaires, the higher score represented 'Worsened'. Missing data were replaced by the valid post-baseline assessment before. The FACT-L score ranges from 0 to 136, with higher scores indicating better quality of life.

Outcome measures

Outcome measures
Measure	Erlotinib n=57 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=55 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire LCS, Cycle 3 (n=42,30)	11.0 units on a scale Standard Deviation 3.1	10.5 units on a scale Standard Deviation 3.2
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire LCS, Cycle 5 (n=28,21)	10.8 units on a scale Standard Deviation 3.0	10.0 units on a scale Standard Deviation 3.9
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire PWB, Baseline (n=56,53)	6.8 units on a scale Standard Deviation 4.0	6.2 units on a scale Standard Deviation 3.7
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire PWB, Cycle 2 (n=52,42)	8.1 units on a scale Standard Deviation 3.7	7.5 units on a scale Standard Deviation 4.4
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire PWB, Cycle 3 (n=41,28)	8.9 units on a scale Standard Deviation 4.3	5.7 units on a scale Standard Deviation 4.2
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire PWB, Cycle 4 (n=37,28)	9.4 units on a scale Standard Deviation 4.0	7.8 units on a scale Standard Deviation 6.1
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire PWB, Cycle 5 (n=30,22)	8.8 units on a scale Standard Deviation 4.3	7.7 units on a scale Standard Deviation 5.5
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire PWB, Cycle 6 (n=25,20)	9.3 units on a scale Standard Deviation 5.0	6.4 units on a scale Standard Deviation 5.5
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire PWB, End of Study (n=52,48)	10.8 units on a scale Standard Deviation 5.2	7.8 units on a scale Standard Deviation 4.5
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire SWB, Baseline (n=55,53)	15.9 units on a scale Standard Deviation 6.3	15.2 units on a scale Standard Deviation 6.8
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire SWB, Cycle 2 (n=52,40)	15.5 units on a scale Standard Deviation 6.7	14.7 units on a scale Standard Deviation 7.2
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire SWB, Cycle 3 (n=42,30)	16.0 units on a scale Standard Deviation 6.9	16.5 units on a scale Standard Deviation 6.8
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire SWB, Cycle 4 (n=37,27)	15.9 units on a scale Standard Deviation 7.0	16.1 units on a scale Standard Deviation 7.1
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire SWB, Cycle 5 (n=28,21)	15.7 units on a scale Standard Deviation 7.0	15.1 units on a scale Standard Deviation 7.7
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire SWB, Cycle 6 (n=26,18)	15.2 units on a scale Standard Deviation 7.8	17.4 units on a scale Standard Deviation 7.1
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire SWB, End of Study (n=52,47)	14.4 units on a scale Standard Deviation 7.1	14.3 units on a scale Standard Deviation 7.6
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire EWB, Baseline (n=57,55)	7.8 units on a scale Standard Deviation 3.7	6.5 units on a scale Standard Deviation 3.4
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire EWB, Cycle 2 (n=52,43)	6.7 units on a scale Standard Deviation 3.8	5.9 units on a scale Standard Deviation 3.2
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire EWB, Cycle 3 (n=42,29)	6.4 units on a scale Standard Deviation 3.5	5.6 units on a scale Standard Deviation 2.8
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire EWB, Cycle 4 (n=37,27)	7.0 units on a scale Standard Deviation 3.6	6.0 units on a scale Standard Deviation 4.6
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire EWB, Cycle 5 (n=29,21)	6.3 units on a scale Standard Deviation 3.6	5.5 units on a scale Standard Deviation 4.7
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire EWB, Cycle 6 (n=25,20)	6.5 units on a scale Standard Deviation 3.5	4.8 units on a scale Standard Deviation 3.1
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire EWB, End of Study (n=52,50)	7.1 units on a scale Standard Deviation 4.1	6.0 units on a scale Standard Deviation 3.4
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire FWB, Baseline (n=56,55)	12.3 units on a scale Standard Deviation 6.2	13.3 units on a scale Standard Deviation 7.4
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire FWB, Cycle 2 (n=51,41)	12.9 units on a scale Standard Deviation 7.1	12.9 units on a scale Standard Deviation 7.1
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire FWB, Cycle 3 (n=41,27)	13.0 units on a scale Standard Deviation 7.4	12.9 units on a scale Standard Deviation 6.9
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire FWB, Cycle 4 (n=37,26)	12.8 units on a scale Standard Deviation 7.2	11.3 units on a scale Standard Deviation 7.8
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire FWB, Cycle 5 (n=29,22)	12.7 units on a scale Standard Deviation 6.2	12.0 units on a scale Standard Deviation 7.6
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire FWB, Cycle 6 (n=25,20)	11.7 units on a scale Standard Deviation 6.4	11.4 units on a scale Standard Deviation 6.3
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire FWB, End of Study (n=51,50)	11.1 units on a scale Standard Deviation 7.2	11.5 units on a scale Standard Deviation 7.2
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire LCS, Baseline (n=56,54)	11.0 units on a scale Standard Deviation 3.2	11.1 units on a scale Standard Deviation 3.8
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire LCS, Cycle 2 (n=50,45)	10.8 units on a scale Standard Deviation 3.1	11.2 units on a scale Standard Deviation 3.5
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire LCS, Cycle 4 (n=37,27)	11.3 units on a scale Standard Deviation 3.1	10.2 units on a scale Standard Deviation 3.2
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire LCS, Cycle 6 (n=26,20)	10.4 units on a scale Standard Deviation 2.9	9.9 units on a scale Standard Deviation 4.0
Quality of Life as Measured by the Functional Assessment of Cancer Therapy (FACT) Questionnaire LCS, End of Study (n=52,50)	11.1 units on a scale Standard Deviation 3.2	10.8 units on a scale Standard Deviation 3.2

SECONDARY outcome

Timeframe: Baseline and Day 1 of Cycles 2, 3, 4, 5, 6 and End of study

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

The FACT Questionnaire contains 4 general and 1 lung cancer symptom-specific subscale, including PWB, SWB, EWB, FWB, and the 8-item LCS that assess symptoms commonly reported by participants with lung cancer. Each subscale was assessed by a five-point scale from 0 (not at all) to 4 (very much) to determine the quality of life. PWB, SWB and FWB scores ranged from 0-28 and EWB scores ranged from 0-24. LCS scores ranged from 0-36. For subscales of FWB and SWB, questionnaires of EWB, and additional concerns questions, the higher score represented 'Improved'. For other subscales and questionnaires, the higher score represented 'Worsened'. Missing data were replaced by the valid post-baseline assessment before. For PWB, FWB, SWB, and EWB scores and disease-specific subscale score, response of down, up or no change were defined as score changes of less than or equal to (≤)2, greater than or equal to (≥)+2, or between these values.

Outcome measures

Outcome measures
Measure	Erlotinib n=52 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=48 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Changes in Quality of Life as Measured by the FACT Questionnaire SWB, Endpoint (n=50,45)	14.3 units on a scale Standard Deviation 7.2	14.4 units on a scale Standard Deviation 7.7
Changes in Quality of Life as Measured by the FACT Questionnaire PWB, Baseline (n=51,45)	6.5 units on a scale Standard Deviation 3.8	6.0 units on a scale Standard Deviation 3.4
Changes in Quality of Life as Measured by the FACT Questionnaire PWB, Endpoint (n=51,45)	10.8 units on a scale Standard Deviation 5.2	7.8 units on a scale Standard Deviation 4.6
Changes in Quality of Life as Measured by the FACT Questionnaire Change in PWB (n=51,45)	4.3 units on a scale Standard Deviation 5.5	1.8 units on a scale Standard Deviation 4.7
Changes in Quality of Life as Measured by the FACT Questionnaire SWB, Baseline (n=50,45)	15.8 units on a scale Standard Deviation 6.5	15.4 units on a scale Standard Deviation 6.7
Changes in Quality of Life as Measured by the FACT Questionnaire Change in SWB (n=50,45)	-1.5 units on a scale Standard Deviation 4.8	-1.0 units on a scale Standard Deviation 6.0
Changes in Quality of Life as Measured by the FACT Questionnaire EWB, Baseline (n=52,48)	7.9 units on a scale Standard Deviation 3.7	6.2 units on a scale Standard Deviation 3.2
Changes in Quality of Life as Measured by the FACT Questionnaire EWB, Endpoint (n=52,48)	7.1 units on a scale Standard Deviation 4.1	6.0 units on a scale Standard Deviation 3.4
Changes in Quality of Life as Measured by the FACT Questionnaire Change in EWB (n=52,48)	-0.8 units on a scale Standard Deviation 4.4	-0.2 units on a scale Standard Deviation 4.0
Changes in Quality of Life as Measured by the FACT Questionnaire FWB, Baseline (n=51,48)	12.6 units on a scale Standard Deviation 6.2	13.4 units on a scale Standard Deviation 7.4
Changes in Quality of Life as Measured by the FACT Questionnaire FWB, Endpoint (n=51,48)	11.1 units on a scale Standard Deviation 7.2	11.7 units on a scale Standard Deviation 7.2
Changes in Quality of Life as Measured by the FACT Questionnaire Change in FWB (n=51,48)	-1.5 units on a scale Standard Deviation 5.1	-1.7 units on a scale Standard Deviation 6.0
Changes in Quality of Life as Measured by the FACT Questionnaire LCS, Baseline (n=51,47)	10.9 units on a scale Standard Deviation 3.3	11.2 units on a scale Standard Deviation 4.0
Changes in Quality of Life as Measured by the FACT Questionnaire LCS, Endpoint (n=51,47)	11.2 units on a scale Standard Deviation 3.2	10.7 units on a scale Standard Deviation 3.0
Changes in Quality of Life as Measured by the FACT Questionnaire Change in LCS (n=51,47)	0.3 units on a scale Standard Deviation 3.3	-0.4 units on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: Baseline and End of study

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

The FACT and the FACT-L contain 4 general and 1 lung cancer symptom-specific subscale, including PWB, SWB, EWB, FWB, and the 8-item LCS that assess symptoms commonly reported by participants with lung cancer. For subscales of FWB and SWB, questionnaires of EWB, and additional concerns questions, the higher score represented 'Improved'. For other subscales and questionnaires, the higher score represented Worsened'. For PWB, FWB, SWB, and EWB scores and disease-specific subscale score, higher scores indicated a better outcome; a response of down, up, or no change was defined as a score change of ≤ -2 (score down), ≥ +2 (score up), or between these values.

Outcome measures

Outcome measures
Measure	Erlotinib n=52 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=48 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change SWB, No Change (n=50,45)	40.0 percentage of participants	40.0 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change SWB, Score Down (n=50,45)	40.0 percentage of participants	37.8 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change SWB, Score Up (n=50,45)	20.0 percentage of participants	22.2 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change EWB, Score Down (n=52,48)	38.5 percentage of participants	33.3 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change EWB, No Change (n=52,48)	38.5 percentage of participants	41.7 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change EWB, Score Up (n=52,48)	23.1 percentage of participants	25.0 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change PWB, Score Down (n=51,45)	7.8 percentage of participants	22.2 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change PWB, No Change (n=51,45)	33.3 percentage of participants	31.1 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change PWB, Score Up (n=51,45)	58.8 percentage of participants	46.7 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change FWB, Score Down (n=51,48)	41.2 percentage of participants	41.7 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change FWB, No Change (n=51,48)	33.3 percentage of participants	35.4 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change FWB, Score Up (n=51,48)	25.5 percentage of participants	22.9 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change LCS, Score Down (n=51,47)	17.6 percentage of participants	31.9 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change LCS, No Change (n=51,47)	47.1 percentage of participants	40.4 percentage of participants
Percentage of Participants With Changes in Quality of Life as Measured by FACT Questionnaire Scores by Category of Change LCS, Score Up (n=51,47)	35.3 percentage of participants	27.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Day 1 of Cycles 2, 3, 4, 5, 6 and End of study

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

The LCS consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition) rated on a five-point scale from 0 (not at all) to 4 (very much). The LCS total score is the sum of the scores from the 7 items. For clear thinking and good appetite, the higher score represented 'Improved'; for other subscales and questionnaires, the higher score represented 'Worsened'. Missing data were replaced by the valid post-baseline assessment before. The change of FACT-L subscore was the change from baseline to endpoint. The LCS of FACT-L is an independently validated tool that measures the disease-related symptoms of lung cancer on an overall scale of 0 (most symptomatic) to 28 (asymptomatic).

Outcome measures

Outcome measures
Measure	Erlotinib n=52 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=48 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Clear thinking, Endpoint (n=52,48)	2.2 units on a scale Standard Deviation 1.3	2.4 units on a scale Standard Deviation 1.3
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Clear thinking, Change (n=52,48)	-0.2 units on a scale Standard Deviation 1.1	0.1 units on a scale Standard Deviation 1.5
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Coughing, Endpoint (n=52,48)	1.4 units on a scale Standard Deviation 0.7	1.4 units on a scale Standard Deviation 0.8
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Hair loss, Change (n=52,48)	0.1 units on a scale Standard Deviation 0.8	-0.1 units on a scale Standard Deviation 1.2
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Shortness of breath, Baseline (n=52,48)	1.4 units on a scale Standard Deviation 0.7	1.4 units on a scale Standard Deviation 1.1
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Shortness of breath, Endpoint (n=52,48)	1.6 units on a scale Standard Deviation 1.0	1.3 units on a scale Standard Deviation 0.9
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Shortness of breath, Change (n=52,48)	0.2 units on a scale Standard Deviation 0.8	-0.1 units on a scale Standard Deviation 1.2
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Weight loss, Baseline (n=51,47)	0.6 units on a scale Standard Deviation 0.8	0.8 units on a scale Standard Deviation 1.0
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Weight loss, Endpoint (n=51,47)	0.7 units on a scale Standard Deviation 0.9	0.6 units on a scale Standard Deviation 0.7
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Weight loss, Change (n=51,47)	0.1 units on a scale Standard Deviation 1.0	-0.2 units on a scale Standard Deviation 1.2
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Clear thinking, Baseline (n=52,48)	2.4 units on a scale Standard Deviation 1.2	2.3 units on a scale Standard Deviation 1.3
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Coughing, Baseline (n=52,48)	1.3 units on a scale Standard Deviation 0.6	1.4 units on a scale Standard Deviation 1.0
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Coughing, Change (n=52,48)	0.1 units on a scale Standard Deviation 0.8	-0.0 units on a scale Standard Deviation 1.2
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Hair loss, Baseline (n=52,48)	0.3 units on a scale Standard Deviation 0.6	0.6 units on a scale Standard Deviation 1.1
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Hair loss, Endpoint (n=52,48)	0.4 units on a scale Standard Deviation 0.7	0.4 units on a scale Standard Deviation 0.6
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Good appetite, Baseline (n=52,48)	1.9 units on a scale Standard Deviation 0.9	2.0 units on a scale Standard Deviation 1.2
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Good appetite, Endpoint (n=52,48)	1.7 units on a scale Standard Deviation 1.1	1.7 units on a scale Standard Deviation 1.0
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Good appetite, Change (n=52,48)	-0.3 units on a scale Standard Deviation 0.9	-0.4 units on a scale Standard Deviation 1.3
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Tightness in chest, Baseline (n=52,48)	1.3 units on a scale Standard Deviation 0.8	1.2 units on a scale Standard Deviation 0.9
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Tightness in chest, Endpoint (n=52,48)	1.4 units on a scale Standard Deviation 0.8	1.3 units on a scale Standard Deviation 1.0
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Tightness in chest, Change (n=52,48)	0.1 units on a scale Standard Deviation 0.9	0.1 units on a scale Standard Deviation 1.2
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Easy breathing, Baseline (n=52,48)	1.7 units on a scale Standard Deviation 0.9	1.7 units on a scale Standard Deviation 1.1
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Easy breathing, Endpoint (n=52,48)	1.7 units on a scale Standard Deviation 0.9	1.6 units on a scale Standard Deviation 1.1
Changes in Quality of Life as Assessed by FACT-L (Lung Symptoms) Questionnaire Easy breathing, Change (n=52,48)	-0.1 units on a scale Standard Deviation 1.1	-0.0 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline and End of study

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

The LCS consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition). The LCS total score is the sum of the scores from the 7 items, each rated on a five-point scale from 0 (not at all) to 4 (very much). For clear thinking and good appetite, the higher score represented 'Improved'; for other subscales and questionnaires, the higher score represented 'Worsened'. For each FACT-L question, the response status was defined as down, up, or no change if the score at endpoint was smaller (score down), larger than (score up), or the same as (no change) that at baseline.

Outcome measures

Outcome measures
Measure	Erlotinib n=52 Participants Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=48 Participants Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Tightness in chest, Score Up (n=52,48)	26.9 percentage of participants	22.9 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Shortness of breath, Score Down (n=52,48)	17.3 percentage of participants	18.8 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Shortness of breath, No Change (n=52,48)	51.9 percentage of participants	58.3 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Shortness of breath, Score Up (n=52,48)	30.8 percentage of participants	22.9 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Weight loss, Score Down (n=51,47)	19.6 percentage of participants	31.9 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Weight loss, No Change (n=51,47)	51.0 percentage of participants	44.7 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Weight loss, Score Up (n=51,47)	29.4 percentage of participants	23.4 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Clear thinking, Score Down (n=52,48)	26.9 percentage of participants	27.1 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Clear thinking No Change (n=52,48)	53.8 percentage of participants	43.8 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Clear thinking, Score Up (n=52,48)	19.2 percentage of participants	29.2 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Coughing, Score Down (n=52,48)	21.2 percentage of participants	22.9 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Coughing, No Change (n=52,48)	53.8 percentage of participants	50.0 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Coughing, Score Up (n=52,48)	25.0 percentage of participants	27.1 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Hair loss, Score Down (n=52,48)	13.5 percentage of participants	18.8 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Hair loss, No Change (n=52,48)	65.4 percentage of participants	60.4 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Hair loss, Score Up (n=52,48)	21.2 percentage of participants	20.8 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Good appetite, Score Down (n=52,48)	26.9 percentage of participants	35.4 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Good appetite, No Change (n=52,48)	61.5 percentage of participants	45.8 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Good appetite, Score Up (n=52,48)	11.5 percentage of participants	18.8 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Tightness in chest, Score Down (n=52,48)	17.3 percentage of participants	22.9 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Tightness in chest, No Change (n=52,48)	55.8 percentage of participants	54.2 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Easy breathing, Score Down (n=52,48)	28.8 percentage of participants	22.9 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Easy breathing, No Change (n=52,48)	48.1 percentage of participants	58.3 percentage of participants
Percentage of Participants With Changes in FACT-L (Lung Symptoms) by Category of Change Easy breathing, Score Up (n=52,48)	23.1 percentage of participants	18.8 percentage of participants

Adverse Events

Erlotinib

Serious events: 19 serious events

Other events: 54 other events

Deaths: 0 deaths

Vinorelbine

Serious events: 14 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 1-800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Erlotinib n=55 participants at risk；n=57 participants at risk Participants received erlotinib 150 mg, tablets, orally, once a day until disease progression, unacceptable toxicity, or participant withdrawal.	Vinorelbine n=54 participants at risk；n=57 participants at risk Cycle 1 (21-day cycle): Participants received vinorelbine 60 mg/m\^2 orally on Days 1 and 8, followed by 1 week off. Cycles 2 and beyond (21-day-cycles): Participants received vinorelbine 80 mg/m\^2 (in the absence of Grade 2 AEs) orally, on Days 1 and 8, followed by 1 week off. Treatment continued until disease progression, unacceptable toxicity, or participant withdrawal.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	0.00% 0/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Vascular disorders Hypertension	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	0.00% 0/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Abdominal distension	3.6% 2/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	7.4% 4/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
General disorders Pyrexia	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	14.8% 8/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.6% 2/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	5.6% 3/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
General disorders Fatigue	1.8% 1/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	11.1% 6/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	0.00% 0/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
General disorders Oedema	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	7.4% 4/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Infections and infestations Folliculitis	7.3% 4/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	0.00% 0/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Metabolism and nutrition disorders Decreased appetite	29.1% 16/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	44.4% 24/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Musculoskeletal and connective tissue disorders Back pain	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	3.7% 2/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Nervous system disorders Headache	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	3.7% 2/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Respiratory, thoracic and mediastinal disorders Hiccups	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	0.00% 0/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Skin and subcutaneous tissue disorders Rash	69.1% 38/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	5.6% 3/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Diarrhoea	36.4% 20/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	13.0% 7/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Mouth ulceration	16.4% 9/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	1.9% 1/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Constipation	12.7% 7/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	13.0% 7/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Respiratory, thoracic and mediastinal disorders Mucosal inflammation	9.1% 5/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	1.9% 1/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Psychiatric disorders Insomnia	9.1% 5/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	13.0% 7/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Vomiting	7.3% 4/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	11.1% 6/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Respiratory, thoracic and mediastinal disorders Productive cough	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	3.7% 2/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Blood and lymphatic system disorders Anaemia	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	1.9% 1/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Infections and infestations Conjunctivitis	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	1.9% 1/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Abdominal pain upper	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	7.4% 4/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Nausea	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	9.3% 5/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Gastrointestinal disorders Stomatitis	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	7.4% 4/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.
Infections and infestations Tinea cruris	5.5% 3/55 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.	0.00% 0/54 • Adverse Events were monitored continuously during the study treatment and for 28 days after the last intake of study medication. Only SAE were recorded during post study treatment phase and for 28 days after the last intake of study medication.