Florian Guisier1, Catherine Dubos-Arvis2, Florent Viñas3, Helene Doubre4, Charles Ricordel5, Stanislas Ropert6, Henri Janicot7, Marie Bernardi8, Pierre Fournel9, Régine Lamy10, Maurice Pérol11, Jerome Dauba12, Gilles Gonzales13, Lionel Falchero14, Chantal Decroisette15, Pascal Assouline16, Christos Chouaid3, Olivier Bylicki17. 1. Rouen University Hospital, Pulmonology, Thoracic Oncology and Respiratory Intensive Care Unit & CIC CRB INSERM 1404, Rouen, France. Electronic address: florian.guisier@chu-rouen.fr. 2. Onco-Pneumology Department, Centre François Baclesse, Caen, France. 3. Pneumology Department, Centre Hospitalier Intercommunal de Créteil, Créteil, France. 4. Pneumology Department, Hôpital Foch, Suresnes, France. 5. Pneumology Department, CHU Pontchaillou, Rennes, France. 6. Hôpital Privé, Antony, France. 7. Pneumology Department, CHU de Clermont-Ferrand, Clermont-Ferrand, France. 8. Pneumology Department, CHI Aix-En-Provence, France. 9. Oncology Department, Institut de Cancérologie de la Loire, Saint-Priest-en-Jarez, France. 10. Pneumology Deparment, Centre Hospitalier Bretagne Sud-Lorient, Lorient, France. 11. Thoracic Oncology Department, Centre Léon Bérard, Lyon, France. 12. Pneumology Department, Hôpital Layne, Mont-De-Marsan, France. 13. Pneumology Department, CH les chanaux, Macon, France. 14. Pneumology Department, CH Villefranche-Sur-Saône, France. 15. CH Annecy Genevois, Pringy, France. 16. CH les deux vallées, Longjumeau, France. 17. Pneumology Department, Hôpital d'Instruction des Armées Percy, Clamart, France.
Abstract
INTRODUCTION: 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. 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, and overall survival (OS). RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. 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, and overall survival (OS). RESULTS: 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. CONCLUSIONS: 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.
Authors: Boris Duchemann; Jordi Remon; Marie Naigeon; Lydie Cassard; Jean Mehdi Jouniaux; Lisa Boselli; Jonathan Grivel; Edouard Auclin; Aude Desnoyer; Benjamin Besse; Nathalie Chaput Journal: Transl Lung Cancer Res Date: 2021-06