The goal of this project is to characterize the genetic profile of patients with advanced stage IIIB/IV non-small cell lung cancer (NSCLC) using liquid biopsies

Lung cancers are the first cause of death by cancer in the world. The majority of these patients are diagnosed at a late stage, non-eligible to a curative treatment. Due to tumoral genomic identification, it has been possible to classify NSCLC in molecular subtypes according to molecular abnormalities detection called "drivers" which can be targeted using an appropriate treatment. This change modifies the standard treatments from the very first line of treatment particularly for patients having an EGFR mutation or an ALK or ROS1 rearrangement, with a significant benefit of progression free survival. The French NCI (INCa) recommends to identify genomic alterations of a genes panel including EGFR, KRAS, BRAF, HER2, ALK and ROS1 as well as mutations in MET exon 14. However, all the patients who benefit from a targeted therapy develop resistance after a mean duration of 10-12 months after starting the treatment. In case of progression, the tumour genetic analysis through new biopsies, enables to identify these mechanisms and then to determine if the patient can benefit or not from a third generation molecule active on these mechanisms, and to have a better understanding of the disease evolution.

The detection of these alterations is routinely performed using tissular biopsies but in 10 to 20% of the cases, it is not possible.

The detection of these molecular abnormalities in the plasma, called " liquid biopsy " is a valuable non-invasive complementary approach for these patients. It is presently used in routine for detecting the EGFR mutations at diagnosis as well as for searching EGFR T790M mutation for resistant patients.

The liquid biopsies enable to detect circulating tumoral DNA.

COHORT 1

Inclusion Criteria:

• Patients with histologically confirmed advanced non-small-cell lung carcinoma (stage IIIB/IV) regardless of the mutation status
• Inclusion at the time of diagnostic
• Realization of tumor biopsy at the institution (Centre Léon Bérard) or outside the institution with an available histopathological report
• Age ≥ 18 years
• Covered by a health insurance
• Signed consent

Exclusion Criteria:

- Patients treated before their liquid biopsy

COHORT 2 Inclusion criteria

• Patients with histologically confirmed advanced non-small-cell lung carcinoma (stage IIIB/IV) with one of the following molecular anomalies: Epidermal Growth Factor Receptor (EGFR), B-Raf proto oncogene (BRAF) or Human Epidermal Growth Factor Receptor-2 (HER2) mutations, Anaplatsic Lymphoma Kinase (ALK) or ROS porto-oncogene 1 (ROS1) translocation, Mesenchymal-epithelial transition factor (MET) amplification, RET rearrangement.
• Inclusion at the time of diagnosis
• Realization of tumor biopsy at the institution (Centre Léon Bérard) or outside the institution with an available histopathological report
• Age ≥ 18 years
• Covered by a health insurance
• Signed consent

COHORT 3 Inclusion criteria

• Patients with histologically confirmed advanced non-small-cell lung carcinoma (stage IIIB/IV) whatever the mutational or PD-L1 status.
• Inclusion at the time of immunotherapy treatment initiation (1st or 2nd line)
• Realization of tumor biopsy at the institution (Centre Léon Bérard) or outside the institution with an available histopathological report
• Age ≥ 18 years
• Covered by a health insurance
• Signed consent

Exclusion criteria

- Initiation of immunotherpy before their liquid biopsy

Patients with advanced NSCLC