Trial Outcomes & Findings for LUX-Lung 5: Afatinib Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (NCT NCT01085136)

Last Updated: 2017-04-04

Results Overview

Progression free survival (PFS) time as determined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 from day of randomization until disease progression or death for patients randomised to combination therapy with afatinib plus paclitaxel or to investigator's choice of chemotherapy. Median was calculated from the Kaplan-Meier curve.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1154 participants

Primary outcome timeframe

From randomization until disease progression or death; Up to 32 months

Results posted on

2017-04-04

Participant Flow

PD = Progression Disease

Participant milestones

Participant milestones
Measure	Afatinib Monotherapy (Part A) Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).	Afatinib Plus Paclitaxel (Part B) Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Part A STARTED	1154	0	0
Part A Randomized to Part B	206	0	0
Part A COMPLETED	831	0	0
Part A NOT COMPLETED	323	0	0
Part B STARTED	0	138	68
Part B COMPLETED	0	87	42
Part B NOT COMPLETED	0	51	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Afatinib Monotherapy (Part A) Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).	Afatinib Plus Paclitaxel (Part B) Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Part A Other Adverse event	223	0	0
Part A Protocol Violation	3	0	0
Part A Lost to Follow-up	3	0	0
Part A Refusal to continue trial medication	64	0	0
Part A Other reason not defined above	30	0	0
Part B Other AE	0	29	8
Part B Refusal to continue trial medication	0	12	7
Part B Not treated	0	4	8
Part B Other reason not defined above	0	6	3

Baseline Characteristics

LUX-Lung 5: Afatinib Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Afatinib Monotherapy (Part A) n=1154 Participants Afatinib 50 mg film-coated tablet was orally administered once daily of each 28-day treatment course, with dose reductions to 40 mg/day and 30 mg/day (following the protocol-defined dose reduction scheme).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	741 Participants n=5 Participants
Age, Categorical >=65 years	413 Participants n=5 Participants
Age, Continuous	60.1 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	654 Participants n=5 Participants
Sex: Female, Male Male	500 Participants n=5 Participants
Race/Ethnicity, Customized Eastern Asian	491 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	459 Participants n=5 Participants
Race/Ethnicity, Customized Other	29 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	175 Participants n=5 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) performance score 0	341 Participants n=5 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) performance score 1	691 Participants n=5 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) performance score 2	122 Participants n=5 Participants
Smoking history Never smoked	615 Participants n=5 Participants
Smoking history <15 pack years & stopped >1 year before diagnosis	132 Participants n=5 Participants
Smoking history Other current or ex-smoker	407 Participants n=5 Participants
Histologic classification Adenocarcinoma	985 Participants n=5 Participants
Histologic classification Squamous	90 Participants n=5 Participants
Histologic classification Other	78 Participants n=5 Participants
Histologic classification Missing	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until disease progression or death; Up to 32 months

Population: Randomised Set: This analysis set consist of all randomised patients irrespective of whether treated or not.

Outcome measures

Outcome measures
Measure	Afatinib Plus Paclitaxel (Part B) n=138 Participants Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) n=68 Participants Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Progression Free Survival (Part B)	5.55 Months Interval 5.06 to 6.31	2.89 Months Interval 1.87 to 3.94	—

SECONDARY outcome

Timeframe: From first dose administration until disease progression or death; Up to 51 months

Population: Treated set

Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A. Median was calculated from the Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Afatinib Plus Paclitaxel (Part B) n=1154 Participants Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Progression Free Survival (Part A)	3.15 Months Interval 2.83 to 3.71	—	—

SECONDARY outcome

Timeframe: From randomization until death; Up to 32 months

Population: Randomised Set

Overall survival (OS) as determined by the time from randomization to death in part B. Median was calculated from the Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Afatinib Plus Paclitaxel (Part B) n=138 Participants Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) n=68 Participants Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Overall Survival (Part B)	12.25 Months Interval 10.91 to 14.88	13.08 Months Interval 9.86 to 15.64	—

SECONDARY outcome

Timeframe: Post baseline tumour-imaging was performed at every 6 weeks thereafter until disease progression; upto 51 months

Population: Treated set

Objective response defined as the best overall response of complete response \[CR\]: disappearance of all target lesion \& partial response \[PR\]: ≥30% decrease in the sum of the longest diameter of target lesions , taking as reference the baseline sum longest diameter of Afatinib monotherapy according to RECIST 1.1 for Part A.

Outcome measures

Outcome measures
Measure	Afatinib Plus Paclitaxel (Part B) n=1154 Participants Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Objective Response (Part A)	8.5 Percentage of participants Interval 6.9 to 10.3	—	—

SECONDARY outcome

Timeframe: Post baseline tumour-imaging was performed at every 8 weeks thereafter until disease progression; up to 32 Months

Population: Randomized Set

Objective response (CR, PR) of Afatinib/paclitaxel combination therapy and comparator chemotherapy in Part B after progression in Part A according to RECIST 1.1 .

Outcome measures

Outcome measures
Measure	Afatinib Plus Paclitaxel (Part B) n=138 Participants Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) n=68 Participants Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Objective Response (Part B)	31.2 Percentage of participants Interval 23.6 to 39.6	13.2 Percentage of participants Interval 6.2 to 23.6	—

SECONDARY outcome

Timeframe: From first administration of treatment until 28 days after last drug administration, up to 51 Months (Part A) and from randomization until 28 days after last drug administration of Trial medication, up to 32 Months (Part B)

Population: Treated Set

Safety of Afatinib as indicated by intensity and incidence of adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0 both for Part A and Part B. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).

Outcome measures

Outcome measures
Measure	Afatinib Plus Paclitaxel (Part B) n=1154 Participants Afatinib 40 mg film-coated tablet dose was orally administered once daily of each 28-day treatment course, with dose reductions to 30 mg/day and 20 mg/day (following the protocol defined dose reduction scheme) plus paclitaxel 80 mg/m2 administered via intravenous infusion once weekly (7 weeks on/1 week off; 2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) n=134 Participants Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).	Investigators Choice of Chemotherapy (Part B) n=60 Participants Reference therapy for Part B dose: Depending on schedule Intravenous or oral administration (2 dose reductions were allowed following the protocol defined dose reduction scheme and the current local summary of product characteristics).
Intensity and Incidence of Adverse Events (AEs) for Part A & Part B. Grade 1	8.6 Percentage of participants	4.5 Percentage of participants	8.3 Percentage of participants
Intensity and Incidence of Adverse Events (AEs) for Part A & Part B. Grade 2	28.0 Percentage of participants	26.1 Percentage of participants	26.7 Percentage of participants
Intensity and Incidence of Adverse Events (AEs) for Part A & Part B. Grade 3	41.1 Percentage of participants	44.0 Percentage of participants	38.3 Percentage of participants
Intensity and Incidence of Adverse Events (AEs) for Part A & Part B. Grade 4	4.9 Percentage of participants	9.7 Percentage of participants	6.7 Percentage of participants
Intensity and Incidence of Adverse Events (AEs) for Part A & Part B. Grade 5	16.6 Percentage of participants	12.7 Percentage of participants	6.7 Percentage of participants

Adverse Events

Afatinib Monotherapy (Part A)

Serious events: 471 serious events

Other events: 1129 other events

Deaths: 0 deaths

Afatinib Plus Paclitaxel (Part B)

Serious events: 54 serious events

Other events: 128 other events

Deaths: 0 deaths

Investigators Choice of Chemotherapy (Part B)

Serious events: 19 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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