*2.1. Study Population and Samples*

The Fondazione IRCCS Istituto Nazionale dei Tumori (Milan, Italy), the Regina Elena National Cancer Institute (Rome, Italy), the Hospital Papa Giovanni XXIII (Bergamo, Italy), and the Metropolitan and Attikon Hospitals (Athens, Greece) were the centers involved. Consecutive patients with metastatic NSCLC who received platinum-based chemotherapy in combination with either vinorelbine, gemcitabine, or pemetrexed, according to the physician's choice, as first-line therapy between February 2014 and April 2017 were included in the BioRaRe prospective multicenter trial.

All patients had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) between 0 and 2 and were at least 18 years of age. Exclusion criteria included any evidence of serious comorbidities that the investigator judged as a contraindication to the participation in the study, pregnancy, and breast-feeding.

Patients evaluable for tumor response according to the RECIST 1.1 criteria were examined, and their demographics and clinical and pathological characteristics were retrieved. E-CRF and medical records were used to collect data.

The study was approved by the Fondazione IRCCS Istituto Nazionale dei Tumori Institutional Review Board (INT18/13) and conducted according to the Declaration of Helsinki ethical principles for medical research involving human subjects. All patients gave signed written informed consent.
