Efficacy and Safety of Anti–PD-1 Immunotherapy in Patients With Advanced NSCLC With BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018

• Published in: Journal of thoracic oncology 2020-04, Vol.15 (4), p.628-636
• Main Authors: Guisier, Florian, Dubos-Arvis, Catherine, Viñas, Florent, Doubre, Helene, Ricordel, Charles, Ropert, Stanislas, Janicot, Henri, Bernardi, Marie, Fournel, Pierre, Lamy, Régine, Pérol, Maurice, Dauba, Jerome, Gonzales, Gilles, Falchero, Lionel, Decroisette, Chantal, Assouline, Pascal, Chouaid, Christos, Bylicki, Olivier
• Format: Article
• Language: English
• Subjects: Aged; BRAF mutations; Female; HER2 mutation; Humans; Immunotherapy; Life Sciences; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; MET mutation; Mutation; Non−small cell lung cancer; PD-1 inhibitors; Prospective Studies; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins c-ret - genetics; RET translocation; Retrospective Studies
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2019.12.129

Immune-checkpoint inhibitor (ICI) efficacy in patients with NSCLC harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF-, HER2-, MET-, and RET-NSCLC in a real-world setting. 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, and overall survival (OS). There were 107 patients with NSCLC (mean age, 65.5 y) included from 21 centers: 37% were never-smokers, 54% were men, and 93% had adenocarcinoma. Among them, 44 had BRAF mutation (V600: 26), 23 had HER2 mutation, 30 had MET mutation, and nine had RET translocation. Programmed cell death ligand 1 (PD-L1) status was known for 70 patients and was greater than or equal to 1% in 34 patients. Before ICI, patients had received a median of one treatment line. Median duration of response, PFS, and OS were 15.4 (95% confidence interval [CI]: 12.6–not reached [NR]) months, 4.7 (95% CI: 2.3–7.4) months, and 16.2 (95% CI: 12.0–24.0) months, respectively, for the entire cohort. The response rates for BRAF-V600, BRAF–non-V600, HER2, MET, and RET-altered NSCLC were 26%, 35%, 27%, 36%, and 38%, respectively. For patients who were PD-L1 negative and those who were PD-L1 positive, PFS was 3.0 (95% CI: 1.2–NR) and 4.3 (95% CI: 2.1–8.5) months, respectively, and OS was 11.7 (95% CI: 4.1–NR) and 35.8 (95% CI: 9.0–35.2) months, respectively. Toxicities were reported in 28 patients (26%), including 11 patients (10%) with a grade greater than or equal to three. In this real-world setting, ICI efficacy against patients with BRAF-, HER2-, MET-, or RET-NSCLC seemed close to that observed in unselected patients with NSCLC. Large prospective studies on these subsets of patients are needed.