Algorithme thérapeutique des CBNPC sans anomalie moléculaire actionnable au-delà de la première ligne

Abstract

Despite the improved results of first-line treatment of metastatic non-small-cell lung carcinoma with anti PD-(L)1, the majority of patients continue to experience disease progression, reflecting primary or acquired resistance to immunotherapy. “Second-line” treatment follows anti PD-(L)1 immunotherapy and platinum-based doublet chemotherapy, administered either sequentially or concomitantly. The multiplicity of mechanisms of resistance to immunotherapy makes it difficult to identify them at the level of a given patient; the majority of therapeutic strategies developed in the second-line setting are therefore agnostic of the mechanism of resistance to immunotherapy. Despite the development of numerous innovative strategies, treatment remains based on cytotoxic chemotherapy, mainly taxanes as monotherapy or combined with anti-angiogenic agents. It remains important to check the absence of genomic or phenotypic alterations that could be accessible to a specific treatment, particularly in the context of a clinical trial. For the time being, the development of conjugated antibodies has not transformed the second-line strategy, and is now mainly conducted in the first-line setting. Rechallenge with immunotherapy can only be envisaged after anti PD-(L)1 has been discontinued due to toxicity, or after the scheduled end of first-line treatment, after a free interval. New strategies are currently being studied to overcome primary or acquired resistance to immunotherapy.