Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Afatinib

Erlotinib Hydrochloride

Gefitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients will be treated with investigator's choice of chemotherapy

Patients will be treated with BIBW 2992daily with a medium dose and weekly administration of Paclitaxel at a dose of 80 mg/m2

BIBW 2992 in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy

Investigator´s choice of chemotherapy

BIBW 2992 will be given in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy

BIBW 2992

Boehringer Ingelheim

The primary objective of this randomized, open-label, active-controlled, multi-center trial is to determine the efficacy of BIBW 2992 given as an add-on to chemotherapy in patients with NSCLC Stage IIIb or IV progressing after BIBW 2992 monotherapy compared to chemotherapy alone in this patient population. Patients on both treatment arms will receive best supportive care in addition to study treatment. Patients enrolled into the trial will be treated and followed until death or lost to follow-up. Additional information on the health-related quality of life (HRQOL) will be collected.

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

Phase III Randomized Trial of BIBW 2992 Plus Weekly Paclitaxel Versus Investigator's Choice of Chemotherapy Following BIBW 2992 Monotherapy in Non-small Cell Lung Cancer Patients Failing Previous Erlotinib or Gefitinib Treatment (LUX Lung 5)

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.

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.

Overall survival (OS) as determined by the time from randomization to death in part B.

Median was calculated from the Kaplan-Meier curve.

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.

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 .

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).

Part A-events that started within the period defined by the first administration of afatinib until randomization into Part B or 28 days after the last administration of afatinib, whichever occurred first. Part B-events that started within the period from randomization through 28 days after the last administration of trial medication.

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 Monotherapy (Part A)

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).

Afatinib Plus Paclitaxel (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)

Age, Categorical

Age, Continuous

Sex: Female, Male

Eastern Asian

Caucasian

Other

Unknown

Race/Ethnicity, Customized

Subjects were graded based on following ECOG PS grade criteria: Grade 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of a light nature. Grade 2: Ambulatory \& capable of all selfcare but unable to carry out any work activities. Up \& about more than 50% of waking hours. Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. Grade 4: Completely disabled. Totally confined to bed or chair. Grade 5: Dead.

Baseline Eastern Cooperative Oncology Group (ECOG) performance score

Never smoked

<15 pack years & stopped >1 year before diagnosis

Other current or ex-smoker

Smoking history

Adenocarcinoma

Squamous

Missing

Histologic classification

Treated set, i.e. all patients who were documented to have taken at least 1 dose of afatinib 50 mg in Part A of the trial and all patients who received at least 1 dose of trial medication in Part B.

Boehringer Ingelheim Call Center

Hazard ratio is calculated from Cox proportional hazard model with treatment as the only factor, stratified by gender and maximum duration of erlotinib or gefitinib (\<6 months vs \>=6 months).

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

Progression Free Survival (Part B)

Progression Free Survival (Part A)

Hazard ratio was calculated from Cox proportional hazard model with treatment as the only factor, stratified by gender and maximum duration of erlotinib or gefitinib (\<6 months vs \>=6 months).

Overall Survival (Part B)

Objective Response (Part A)

Odds ratio, 95% Confidence Interval (CI) and p-value (two-sided) from logistic regression stratified for maximum treatment duration of prior erlotinib or gefitinib (\>=6 months vs \<6 months) and gender.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT01085136	Carcinoma, Non-...	Investigator´s ... BIBW 2992	18 Years -	Boehringer Ingelheim
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	NCT01085136	Carcinoma, Non-...	Investigator´s ... BIBW 2992	18 Years -	Boehringer Ingelheim

Spots Global Cancer Trial Database for investigator´s choice of chemotherapy