Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Adenocarcinoma of Lung

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Lung Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Gemcitabine

Cisplatin

Afatinib

Antimetabolites

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity

Patients receive Gemcitabine and Cisplatin, maximum is 6 courses

Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.

Gemcitabine+Cisplatin

starting dose is 40 mg, in the event of no or minimal drug-related adverse events after one course, the dose will be increased to 50mg. in the event of certain drug related Adverse Event (AE), dose reduction will be increments of 10 mg, with the lowest dose being 20mg.

BIBW 2992

Boehringer Ingelheim

To investigate the efficacy and safety of BIBW 2992 compared to standard first-line chemotherapy in patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation

BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)

LUX-Lung 6: A Randomized, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation

The primary endpoint was progression-free survival (PFS) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival was defined as the time from randomisation to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not have a PFS.

Only data collected up until the analysis cut-off date (27 December 2013) were considered. Median time results from unstratified Kaplan-Meier estimates.

OR is defined as a best overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with OR.

CR is defined as the disappearance of all target lesions and non-target lesions and no new lesions.

PR is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD, non-Progressive Disease or non evaluation of all non-target lesions and no new lesions.

(Exact 95% Confidence interval by Clopper and Pearson.)

DC is defined as a patient with objective response (OR) or stable disease (SD) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with DC.

OS is defined as the time from randomisation to death. For patients who had not died until 7 December 2017, the date they were last known to be alive was derived from patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date.

Median time results from unstratified Kaplan-Meier estimates.

OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1.

For patients with an objective response, time to objective response was defined as the time from randomisation to the first objective response.

Outcome data are the percentage of patients with OR by each scheduled tumour assessment.

OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1.

For patients with an objective response, duration of objective response was defined as the time from the first objective response to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.

For patients with disease control, duration of disease control was defined as the time from randomisation to progression or death whichever occurs first. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.

Tumour shrinkage is calculated as the minimum post-baseline sum of longest diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) (SLD), as assessed by central independent review. The mean of these minimum values are presented after adjusting for baseline sum of longest diameters and EGFR mutation category. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered. A negative value means the smallest post-baseline SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline.

The means are adjusted for baseline sum of lesions and EGFR mutation category.

The change from baseline to the lowest and the last body weight recorded or during the the study.

The last ECOG performance score category recorded during the study. Outcome data are the percentage of patients with an shift of ECOG performance status from baseline to the last ECOG performance status.

ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction;

1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work;
2. Ambulatory (\>50 percent of waking hours), capable of all selfcare, unable to carry out any work activities;
3. Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours;
4. Completely disabled, cannot carry on any selfcare, totally confined to bed or chair;
5. Dead

HRQOL as measured by standardised questionnaires (EuropeanOrganisation for Research and Treatment of Cancer (EORTC)) quality of life questionaires (OLQ-C30) and its lung cancer module (QLQ-LC13). Analysis for cough: QLQ-LC13, question 1.

Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.

HRQOL as measured by OLQ-C30 and its lung cancer module (QLQ-LC13). Analysis for dyspnoea: composite of QLQ-LC13, questions 3 to 5; individual item from QLQ-C30, question 8.

Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.

HRQOL as measured by OLQ-C30 and its lung cancer module QLQ-LC13. Analysis for pain: composite of QLQ-C30, questions 9 and 19; individual items from QLQ-LC13, questions 10, 11 and 12.

Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.

Outcome data are the trough plasma concentrations of afatinib at day 22 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the Pharmacokinetics (PK) assessment period).

Outcome data are the trough plasma concentrations of afatinib at day 29 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).

Outcome data are the trough plasma concentrations of afatinib at day 43 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).

Safety of Afatinib as indicated by intensity and incidence of adverse events graded according to the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Presented as the percentage of patients with an Adverse Events during the on-treatment period by highest CTCAE grade.

Outcome data presented are the percentage of patients by worst CTCAE grade (only Grades 2 to 4 presented) on treatment for the following laboratory parameters: Potassium, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine and Creatine Kinase.

For Potassium; only CTCAE grades resulting from hypokalemia (low values) are presented.

The treated set (TS) included all randomised patients documented to have taken at least 1 dose of study medication. Analysis of Adverse Events (AEs) was based on the concept of treatment-emergent AEs. AEs with onset after the first administration of study drug and within 28 days after the last administration were considered to be on-treatment.

Patients received Afatinib film-coated tablets 40 mg once daily (q.d.) orally with possible dose escalation to 50 mg q.d. and dose reduction to 40 mg q.d. (if applicable), 30 mg q.d., or 20 mg q.d. (according to the protocol-defined dose-escalation and dose-reduction scheme), if required. No dose increase was allowed after dose reduction. Each treatment course was planned to be 21 days. For afatinib, patients received continuous daily dosing until disease progression, unacceptable adverse events (AEs) occurred, or withdrawal of consent for any reason.

Afatinib 40 Milligram (mg)

Patients received Gemcitabine (lyophilised powder) 1000 milligram per square metre (mg/m²) as an intravenous infusion over 30 minutes on day 1 and day 8, cisplatin (solution for infusion) 75 mg/m² as an intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles; Chemotherapy could be delayed or the dose could be reduced in accordance with the guidance in the current summary of product characteristics. For gemcitabine / cisplatin, patients were to receive a maximum of 6 treatment courses unless they developed disease progression, experienced unacceptable AEs, or withdrawal of consent for any reason.

Gemcitabine / Cisplatin Chemotherapy

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

EGFR mutation group (L858R / Deletion Exon 19 / other) was a stratification factor.

Epidermal growth factor receptor (EGFR)

ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work; 2=Ambulatory (\>50 percent of waking hours), capable of all selfcare, unable to carry out any work activities; 3=Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours; 4=Completely disabled, cannot carry on any selfcare, totally confined to bed or chair; 5=Dead

Eastern Cooperative Oncology Group (ECOG) performance status (PS)

The randomised set (RS) included all patients randomised to receive treatment, whether treated or not.

Boehringer Ingelheim, Call Center

A stratified log-rank test (by the epidermal growth factor receptor (EGFR) mutation category stratification factor used at randomisation) was used to test for the effect of afatinib on PFS compared with gemcitabine / cisplatin chemotherapy.

A Cox proportional-hazards model, stratified by EGFR mutation category was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) between the 2 treatment arms.

Progression-free Survival

A logistic regression model, stratified by EGFR mutation category was used to compare the objective response rate between the 2 treatment arms.

Objective Response (OR)

Disease Control (DC)

A stratified log-rank test (by the epidermal growth factor receptor (EGFR) mutation category stratification factor used at randomisation) was used to test for the effect of afatinib on OS compared with gemcitabine / cisplatin chemotherapy.

A Cox proportional hazard model stratified (by EGFR mutation category stratification factor used at randomisation) was used to test the effect of afatinib on OS compared with gemcitabine / cisplatin chemotherapy.

Overall Survival (OS)

By Week 6

By Week 12

By Week 18

By Week 24

By Week 30

By Week 36

By Week 42

By Week 48

By Week 60

By Week 72

By Week 84

By Week 96

By Week 108

By Week 120

The RS included all patients randomised to receive treatment, whether treated or not.

Time to Objective Response (OR)

The Randomised set with an objective response.

Duration of Objective Response

Duration of Disease Control

The randomised set. There were ony 220 patients in the Afatinib arm and 101 patients in the Gemcitabine / Cisplatin arm with baseline and post-baseline target lesion measurements.

Tumour Shrinkage

Change from baseline at lowest value

Change from baseline at last value

The randomised set. Data only presented for a patient with a baseline and at least on post-baseline assessment of weight.

Change From Baseline in Body Weight

ECOG PS 0 (baseline) 0 (last value)

ECOG PS 1 (baseline) 0 (last value)

ECOG PS 0 (baseline) 1 (last value)

ECOG PS 1 (baseline) 1 (last value)

ECOG PS 0 (baseline) 2 (last value)

ECOG PS 1 (baseline) 2 (last value)

ECOG PS 0 (baseline) 3 (last value)

ECOG PS 1 (baseline) 3 (last value)

ECOG PS 0 (baseline) 4 (last value)

ECOG PS 1 (baseline) 4 (last value)

The randomised set. Data only presented for patients with a baseline and at least one post-baseline assessment of ECOG status.

Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

A stratified log-rank test (by the epidermal growth factor receptor (EGFR) mutation category stratification factor used at randomisation) was used to test for the effect of afatinib on HRQOL compared with gemcitabine / cisplatin chemotherapy.

Cox proportional hazard model stratified by EGFR mutation group

Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing

Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea

Health Related Quality of Life (HRQOL): Time of Deterioration in Pain

Patients receiving Afatinib 30mg once daily (q.d.) orally after a dose reduction.

Afatinib 30mg q.d.

Patients receiving Afatinib 40mg once daily (q.d.) orally

Afatinib 40mg q.d.

Patients receiving Afatinib 50mg once daily (q.d.) orally after a dose escalation.

Afatinib 50mg q.d.

All patients who had at least 1 afatinib dose and who had at least 1 valid afatinib plasma concentration available.

Pharmacokinetics of Afatinib at Day 22

Patients receiving Afatinib 30mg once daily (q.d.) after a dose reduction.

Patients receiving Afatinib 40mg once daily (q.d.)

Patients receiving Afatinib 50mg once daily (q.d.) after a dose escalation.

Pharmacokinetics of Afatinib at Day 29

Pharmacokinetics of Afatinib at Day 43

CTCAE Grade 1

CTCAE Grade 2

CTCAE Grade 3

CTCAE Grade 4

CTCAE Grade 5

The treated set (TS) included all randomised patients who were documented to have taken at least 1 dose of study medication (i.e. afatinib or gemcitabine / cisplatin). Patients were allocated according to the treatment actually received.

Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events

Potassium CTCAE grade 2

Potassium CTCAE grade 3

Potassium CTCAE grade 4

AST CTCAE grade 2

AST CTCAE grade 3

AST CTCAE grade 4

ALT CTCAE grade 2

ALT CTCAE grade 3

ALT CTCAE grade 4

Creatinine CTCAE grade 2

Creatinine CTCAE grade 3

Creatinine CTCAE grade 4

Creatinine Kinase CTCAE grade 2

Creatinine Kinase CTCAE grade 3

Creatinine Kinase CTCAE grade 4

Treated set (TS) included all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated according to the treatment actually received. Patients with a baseline and at least one on-treatment assessment of the parameter are of interest.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)	NCT01121393	Carcinoma, Non-... Adenocarcinoma	Gemcitabine+Cis... BIBW 2992	18 Years -	Boehringer Ingelheim
BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)	NCT01121393	Carcinoma, Non-... Adenocarcinoma	Gemcitabine+Cis... BIBW 2992	18 Years -	Boehringer Ingelheim

Spots Global Cancer Trial Database for gemcitabine+cisplatin