Algorithme thérapeutique des CBNPC sans anomalie moléculaire actionnable: Therapeutic algorithm for NSCLC without actionable molecular abnormalities

Abstract

The development of immunotherapy in first-line therapy with anti-PD-1 and anti-PD-L1 has changed the first line treatment algorithm of advanced NSCLC. The anti-PD-1 pembrolizumab and cemiplimab clearly improve the overall survival in NSCLC with high PD-L1 expression (≥ 50% of tumour cells), comparatively to cytotoxic chemotherapy. Combinations of anti-PD(L)-1 to platinum-based chemotherapy are superior to chemotherapy alone, independently of PD-L1 level of expression. They represent the 1st line gold-standard when PD-L1 is expressed in less than 50% of tumour cells and might reduce the risk of early disease progression in comparison with pembrolizumab when PD-L1 ≥50%. The room for anti-CTLA-4 + anti-PD(L)-1 combinations which are not available in France remains to be established. Second-line treatment is currently based on chemotherapy, with a platinum-based doublet for patients treated in first line by pembrolizumab alone, and standard second-line chemotherapy options for patients treated by chemotherapy-immunotherapy combinations, i.e. docétaxel regardless of histology or pemetrexed for non-squamous cell carcinoma when not used in first line. Addition of an antiangiogenic agent to docetaxel only achieved a modest improvement of overall survival but neither nintedanib nor ramucirumab are available in France. Immunotherapy still benefits only a minority of patients whose identification is imperfect, underscoring the need for new strategies based on characterizing, initiating, and amplifying the anti-tumour immune response as well as understanding the mechanisms of resistance to treatment in order to improve these results.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.