Rationale: Advanced non-small-cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 14 months when treated with erlotinib. However, the presence of EGFR mutations can only imperfectly predict outcome. The investigators hypothesize that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways. The investigators propose a model of treatment whereby patients with EGFR mutations (single or with T790M) can attain a benefit with longer overall PFS when treated with erlotinib plus bevacizumab. When the patients are grouped by BRCA1 mRNA levels and T790M the hypothesis is that the combination of erlotinib plus bevacizumab can improve the PFS in all subgroups.
Name: Erlotinib
Description: Patients will be treated with erlotinib, 150 mg p.o., dailyType: DrugErlotinib plus bevacizumab
Name: Bevacizumab
Description: Patients will be treated with bevacizumab 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days)Type: DrugErlotinib plus bevacizumab
Description: Time from the date of enrolment until documented progression or death, whichever occurs first.
Measure: Progression free survival Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patientDescription: Time from the date of enrolment to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death).
Measure: Time to treatment failure Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patientDescription: Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment.
Measure: Objective response Time: termination of trial treatmentDescription: Adverse events graded according to NCI CTCAE V4.
Measure: Adverse events Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patientDescription: Achievement of objective response or stable disease for at least 6 weeks.
Measure: Disease control Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patientDescription: Interval from the date of first documentation of objective response by RECIST to the date of first documented progression or relapse.
Measure: Duration of response Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patientDescription: Time from the date of enrolment until death from any cause.
Measure: Overall survival (OS) Time: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patientSingle Group Assignment
There are 2 SNPs
BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC) Rationale: Advanced non-small-cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 14 months when treated with erlotinib. --- L858R ---
- Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R) Exclusion Criteria: - Patients with increased risk of bleeding - Patients with clinically significant cardiovascular diseases - Patients with a history of thrombosis or thromboembolism in the 6 months prior to treatment - Patients with gastrointestinal problems - Patients with neurologic problems - Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma. --- L858R ---
The investigators hypothesize that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways. --- T790M ---
The investigators propose a model of treatment whereby patients with EGFR mutations (single or with T790M) can attain a benefit with longer overall PFS when treated with erlotinib plus bevacizumab. --- T790M ---
When the patients are grouped by BRCA1 mRNA levels and T790M the hypothesis is that the combination of erlotinib plus bevacizumab can improve the PFS in all subgroups. --- T790M ---
To determine long-term outcome of patients with advanced non-squamous NSCLC harbouring EGFR mutations with or without T790M mutation at diagnosis and treated with the combination of erlotinib and bevacizumab. --- T790M ---
Primary endpoint: progression-free survival 2. To evaluate the efficacy and tolerability of the combination 3. To evaluate the correlation of BRCA1 mRNA and AEG-1 mRNA expression and T790M with progression-free survival 4. To monitor EGFR mutations (including T790M) in serum and plasma longitudinally 5. To evaluate molecular biomarkers related to EGFR TKI and bevacizumab Design: This is a multinational, multi-center phase II trial of erlotinib plus bevacizumab in patients with advanced non-squamous NSCLC harbouring EGFR mutations confirmed by central re-assessment. --- T790M ---
Primary endpoint: progression-free survival 2. To evaluate the efficacy and tolerability of the combination 3. To evaluate the correlation of BRCA1 mRNA and AEG-1 mRNA expression and T790M with progression-free survival 4. To monitor EGFR mutations (including T790M) in serum and plasma longitudinally 5. To evaluate molecular biomarkers related to EGFR TKI and bevacizumab Design: This is a multinational, multi-center phase II trial of erlotinib plus bevacizumab in patients with advanced non-squamous NSCLC harbouring EGFR mutations confirmed by central re-assessment. --- T790M --- --- T790M ---
Patients will be stratified into two subgroups, with and without EGFR T790M mutation. --- T790M ---