First-line immunotherapy for lung cancer with MET exon 14 skipping and the relevance of TP53 mutations
Menée en Allemagne à partir de données portant sur 110 patients atteints d'un cancer du poumon non à petites cellules présentant une mutation du gène MET (perte de l’exon 14), cette étude compare l'efficacité, du point de vue de la survie sans progression, du taux de réponse objective et de la survie globale, et la toxicité d'une chimiothérapie et d'une immunothérapie de première ligne, en monothérapie ou en combinaison, en fonction de la présence de mutations au niveau du gène TP53
Background: The efficacy of checkpoint inhibitors for non-small cell lung cancer (NSCLC) with MET exon 14 skipping (MET
Δ14ex) remains controversial. Materials and methods
:
110 consecutive METΔ14ex NSCLC patients receiving first-line chemotherapy (CHT) and/or immunotherapy (IO) in 10 German centers between 2016-2022 were analyzed. Results
:
Combined CHT-IO was given to 35/110 (32%) patients, IO alone to 43/110 (39%), and CHT to 32/110 (29%) upfront. Compared to CHT, CHT-IO showed longer progression-free survival (median PFS 6 vs. 2.5 months, p=0.004), more objective responses (ORR 49% vs. 28%, p=0.086) and numerically longer overall survival (OS 16 vs. 10 months, p=0.240). For IO monotherapy, OS (14 vs. 16 months) and duration of response (26 vs. 22 months) were comparable to those of CHT-IO. Primary progressive disease (PD) was more frequent with IO compared to CHT-IO (13/43 vs. 3/35, p=0.018), particularly for never-smokers (p=0.041). Higher PD-L1 TPS were not associated with better IO outcomes, but TP53 mutated tumors showed numerically improved ORR (56% vs. 32 %, p=0.088) and PFS (6 vs. 3 months, p=0.160), as well as longer OS in multivariable analysis (HR=0.54, p=0.034) compared to their wild-type counterparts. Any second-line treatment was administered to 35/75 (47%) patients, with longer survival for capmatinib or tepotinib compared to crizotinib (PFS 10 vs. 3 months, p=0.013; OS 16 vs. 13 months, p=0.270). Conclusion
:
CHT-IO is superior to CHT, and IO alone also effective for METΔ14ex NSCLC, especially in the presence of TP53 mutations and independent of PD-L1 expression, but never-smokers are at higher risk of primary PD.