A Multicenter Randomized Phase III Study Comparing Second-line Treatment With Chemotherapy Associated or Not to Erlotinib in NSCLC Patients With Secondary Resistance to TKI-EGFR

Inclusion Criteria:

* Man or woman aged 18 years or more
* Non-small cell lung cancer carcinoma (NSCLC) cytologically or histologically confirmed
* Measurable disease according to RECIST 1.1 criteria
* Life expectancy greater than 12 weeks
* Performance Status (ECOG) ≤ 2
* Stage IIIB considered ineligible for thoracic radiotherapy at "curative" doses or stage IV
* Presence of at least one measurable target lesion
* Documented disease progression (RECIST 1.1) after first line treatment with erlotinib, during at least 4 months in case of partial or complete response according to RECIST criteria, or 6 months in case of stable disease. The treatment with Erlotinib should not be discontinued for more than 8 days between the progression and the inclusion in the study. The daily dose of Erlotinib should be at least 50 mg.
* 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.
* Prior radiotherapy is allowed if the volume of irradiated marrow is \<25% of the total bone marrow. The prior radiotherapy must be completed at least two weeks before study entry
* Brain metastases are allowed if they are controlled without steroids and if their treatment is completed (radiotherapy and/or surgery). Patients with no symptomatic brain metastases may be included; even if brain metastases are progressive and even if they are the only site of progression (since the investigator considers that irradiation is not required). These metastases have not to be life-threatening (are excluded: cerebellar metastasis ≥ 2 cm, brainstem metastasis, brain metastasis \> 3 cm and/or near important functional structure).
* Normal Liver function (bilirubin ≤ULN, AST - ALT ≤2.5 x ULN, alkaline phosphatase ≤3 x ULN), or in case of liver metastases: alkaline phosphatase, AST-ALT ≤ 5 x ULN
* Normal renal function: blood creatinine ≤ULN and / or creatinine clearance\> 60 ml/min calculated with the MDRD formula
* Normal blood function: absolute neutrophil count ≥ 1.5 x 109/l and / or platelets ≥ 100 x 109 / l, hemoglobin\> 9 g/dl
* Woman and man under efficient contraception during treatment and at least 6 months after the end of treatment by pemetrexed or platinum or gemcitabine
* Signed written Informed consent

Exclusion Criteria:

* Bronchoalveolar, mixed, neuroendocrine and small cell lung cancers
* Patient with only bone metastases are not eligible
* All progressive metastatic sites treated locally (surgery, radiotherapy)
* Superior vena cava syndrome
* Uncontrolled cardiac disease requiring treatment
* Congestive heart failure, angina pectoris, significant arrhythmias or history of myocardial infarction within the previous 12 months
* Neurological or psychiatric disorders
* Uncontrolled infectious disease
* Peripheral neuropathy grade≥ 2
* Definitive contraindication for the use of steroids
* Inductive anti-epileptic treatments (phenobarbital, phenytoïne)• Previous or concomitant other cancer, including skin cancer (except basal cell cancer of the skin), except in situ treated carcinoma of the cervix , except cancer treated with surgery alone without recurrence for 5 years
* Pregnant or breastfeeding woman
* Patient follow-up not achievable
* Participation in a trial within the last 30 days
* Patient deprived of liberty as a result of a justice or administrative decision