Efficacy and safety of programmed cell-death-protein-1 and its ligand inhibitors in pretreated patients with epidermal growth-factor receptor-mutated or anaplastic lymphoma kinase-translocated lung adenocarcinoma

• Published in: Medicine (Baltimore) Vol. 99; no. 3; p. e18726
• Main Authors: Bylicki, Olivier, Guisier, Florian, Monnet, Isabelle, Doubre, Hélène, Gervais, Radj, Janicot, Henri, Perol, Maurice, Fournel, Pierre, Lamy, Régine, Auliac, Jean-Bernard, Chouaid, Christos
• Format: Journal Article
• Language: English
• Published: United States Lippincott, Williams & Wilkins 01.01.2020; Wolters Kluwer Health
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - genetics; Anaplastic Lymphoma Kinase - genetics; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; Cancer; ErbB Receptors - genetics; Female; France; Humans; Life Sciences; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Male; Middle Aged; Observational Study; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Receptor Protein-Tyrosine Kinases - genetics; Retrospective Studies; Translocation, Genetic; France; programmed cell-death-protein-1 and its ligand inhibitors; c-ros oncogene 1 translocation; anaplastic lymphoma kinase translocation; epidermal growth-factor receptor-activating mutations; immunecheckpoint inhibitors; non-small-cell lung cancer
• ISSN: 0025-7974; 1536-5964
• DOI: 10.1097/MD.0000000000018726

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 epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting.In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK- or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation.Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61% were never-smokers and 59% were women. Among them, 82% had EGFR-activating mutations, 16% ALK translocations, or 2% ROS1 translocations. Before ICI therapy, patients had received a median of 3 treatment lines (including tyrosine-kinase inhibitor). The median PFS was 2.1 (95% confidence interval [CI], 1.5-3.2) months for the entire cohort, 2.2 (95% CI, 1.4-3.2) for EGFR-mutated patients, and 2.4 (95% CI, 2.1-not reached) months for ALK-translocated patients. The median OS was 14.7 (95% CI, 12.1-19.2) months for the entire population and 13.9 (95% CI, 8.8-20.0) and 19.2 (95% CI, 13.1-not reached) months for EGFR-mutated and ALK-translocated patients, respectively. Seven (13.7%) patients were treated with ICI for >9 months. Toxicities were reported in 22% (11/51), including 8% (4/51) grade ≥3.In this real-world setting, analysis of ICI PFS against EGFR-mutated or ALK-translocated NSCLC patients appeared close to that observed in pretreated unselected NSCLC patients. The more promising OS probably linked to post-ICI treatments. Large prospective studies on these patient subsets are needed.