Efficacy and safety of anti-PD-1 immunotherapy in patients with advanced Non Small Cell Lung Cancer with BRAF, HER2 or MET mutation or RET-translocation. GFPC 01-2018
Menée en France dans un contexte de vie réelle sur 107 patients atteints d'un cancer du poumon non à petites cellules et porteurs de mutations BRAF, HER2, MET ou d'une translocation RET (âge moyen : 65,5 ans), cette étude rétrospective multicentrique évalue l'efficacité, du point de vue de la durée du traitement, de la survie sans progression, du taux de réponse objective, de la durée de la réponse et de la survie globale, et la toxicité d'un traitement par inhibiteur de point de contrôle immunitaire
Introduction : Immune-checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC) harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF/HER2/MET/RET-NSCLC in a real-world setting. Methods : In this retrospective, multicenter study in ICI-treated BRAF-, HER2-, MET- or RET-NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, progression-free survival (PFS), objective response rate, duration of response (DoR), and overall survival (OS). Results : 107 NSCLC patients (mean age, 65.5 years) were included from 21 centers: 37% never-smokers, 54% male and 93% with adenocarcinoma. Among them, 44 had BRAF- mutation (V600: 26), 23 HER2 mutation, 30 MET mutation and 9 RET translocation. PDL1 status was known for 45 patients: ≥1% in 34. Before ICI, patients had received a median of one treatment line. Median DoR, PFS and OS were 15.4 (95%CI, 12.6 – NR) months, 4.7 (95%CI, 2.3–7.4) months and 16.2 (95%CI, 12.0 – 24.0) months for the entire cohort, respectively. Response rate for BRAF-V600, BRAF-nonV600, HER2, MET and RET-altered NSCLC was 26%, 33%, 27%, 38% and 38%, respectively. For PDL1 negative and positive patients, PFS was 3.0 (95%CI, 1.2 – NR) and 4.3 (95%CI, 2.1 – 8.5) months, respectively, and OS was 13.3 (95%CI, 4.1 – NR) and 35.2 (95%CI, 9.0 – 35.2) months, respectively. Toxicities were reported in 28 (26%) patients including 11 (10%) grade ≥3. Conclusion : In this real-world setting, ICI efficacy against BRAF-, HER2-, MET- or RET-NSCLC patients appeared close to that observed in unselected NSCLC patients. Large prospective studies on these patient subsets are needed.