The current first line treatment of patients with EGFR activating mutation lung cancer is EGFR TKI. Compared to platinum-based chemotherapy, EGFR-TKIs are superior in terms of response rate and progression-free survival. However, an acquired resistance occurs almost constantly. The second-line treatment includes platinum-based chemotherapy in the absence of contraindication. This chemotherapy is then administered after discontinuing EGFR TKIs. However, a rebound phenomenon of the disease was described in patients who discontinued EGFR TKIs. Some clinical teams therefore recommend, as a precaution, in order to avoid any withdrawal phenomenon, to never discontinue EGFR TKIs in patients developing an EGFR TKI acquired resistance. It seems therefore useful to conduct a study to better define the therapeutic strategy to adopt in patients developing an acquired resistance after having received EGFR TKIs as first line treatment.
Name: ERLOTINIB WITH CHEMOTHERAPY
Name: CHEMOTHERAPY ONLY
Description: Efficacy will be assessed by the PFS, define as time between randomization of the patient in the study and disease progression (local, regional, distant and second cancer) or death (all causes). Alive patients free of progression will be censored at the last follow-up.
Measure: Efficacy by PFS Time: From date of randomization until the date of first documented progression evaluated every 6-9 weeksDescription: difference between the scores of QoL at baseline and at 4 months after inclusion for the three targeted dimensions of EORTC QLQ-C30 (global quality of life, fatigue and physical functioning). A difference or 10 points or more at 4 months after inclusion for one score between the 2 arms will be considered as clinically relevant.
Measure: scores of QoL Time: at 4 months after inclusionDescription: Overall survival defined as time interval between randomization and death (all causes). Alive patients will be censored at the last date of news or data cut off
Measure: Overall survival Time: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 monthsDescription: Tumoral response (complete response, partial response, stable disease, progression) according to RECIST 1.1
Measure: Tumoral response Time: every 6-9 weeksDescription: Toxicities according to NCI-CTC-AE v.4
Measure: Toxicities Time: From date of randomization until study participation, assessed up to 100 monthsDescription: Rebound phenomenon (flare) defined by a hospitalization or a death within 3 weeks for disease progression after the end of TKI EGFR treatment (in the arm without EGFR TKI) and date of onset
Measure: Rebound phenomenon (flare) Time: within 3 weeks after disease progression before inclusionAllocation: Randomized
Parallel Assignment
There are 2 SNPs
- Presence of one of the EGFR activating mutations in the tumor (exon 19 deletion or L858R, G719X or L861Q) - One additional line of previous chemotherapy is allowed if administered in adjuvant or neoadjuvant setting and received more than six months before. --- L858R ---
- Presence of one of the EGFR activating mutations in the tumor (exon 19 deletion or L858R, G719X or L861Q) - One additional line of previous chemotherapy is allowed if administered in adjuvant or neoadjuvant setting and received more than six months before. --- L858R --- --- L861Q ---