Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non–Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis

• Published in: Clinical lung cancer Vol. 20; no. 1; pp. e97 - e106
• Main Authors: Ksienski, Doran, Wai, Elaine S., Croteau, Nicole, Fiorino, Leathia, Brooks, Edward, Poonja, Zia, Fenton, Dave, Geller, Georiga, Glick, Daniel, Lesperance, Mary
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Colitis - diagnosis; Colitis - etiology; Drug-Related Side Effects and Adverse Reactions - diagnosis; Female; Humans; Immune related adverse events; Immunotherapy; Immunotherapy - adverse effects; Immunotherapy - methods; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Middle Aged; Neoplasm Staging; Nivolumab - therapeutic use; Programmed Cell Death 1 Receptor - immunology; Real world data; Retrospective Studies; Survival Analysis; Withholding Treatment; Immune related adverse events; Real world data; Immunotherapy
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2018.09.005

The programmed death 1 antibodies (PD-1 Ab) nivolumab and pembrolizumab improve overall survival (OS) in advanced non–small-cell lung cancer (NSCLC). We evaluated the correlation between immune-related adverse events (irAE) and treatment interruption due to irAE on clinical efficacy of PD-1 Ab in advanced NSCLC. Advanced NSCLC patients treated with PD-1 Ab between June 2015 to November 2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Common Terminology Criteria for Adverse Events, version 4.0) of irAE were abstracted from chart review. Kaplan-Meier curves of OS from initiation of PD-1 Ab were generated. Multivariable analysis with 6- and 12-week landmark analysis was performed by Cox proportional hazard regression models. In a cohort of 271 patients, irAEs were observed in 116 patients (42.8%). Nivolumab recipients developing colitis had lower OS compared to those who did not at the 6-week landmark (P = .010) and 12-week landmark (P = .072). For the entire cohort, 56 patients (20.7%) needed treatment interruption because of an irAE. Treatment interruption correlated with lower OS at the 6-week landmark (P = .005) and 12-week landmark (P = .008). Six-week landmark multivariable analysis identified Charlson Comorbidity Index score of 3 or higher, Eastern Cooperative Oncology Group Performance Status of 2 or higher, presence of liver metastases, and irAE greater than grade 2 versus no irAE to be associated with decreased OS (each P < .05). Treatment interruption due to irAE was associated with a lower median OS compared to continuous PD-1 Ab therapy. Shorter OS seen with severe irAE might reflect the need for improved physician education in irAE treatment algorithms. Nivolumab and pembrolizumab can cause immune-related adverse events (irAE). In this retrospective chart review of advanced non–small-cell lung cancer patients receiving programmed death 1 antibodies in British Columbia, Canada, treatment interruption due to irAE was associated with a lower median overall survival (OS) than those treated continuously. Development of colitis in nivolumab-treated patients was associated with shorter OS than for patients who did not develop colitis.