Association Between Immune-related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Non–small-cell Lung Cancer

• Published in: Clinical lung cancer Vol. 20; no. 3; pp. 201 - 207
• Main Authors: Grangeon, Mathieu, Tomasini, Pascale, Chaleat, Solene, Jeanson, Arnaud, Souquet-Bressand, Maxime, Khobta, Nataliya, Bermudez, Julien, Trigui, Youssef, Greillier, Laurent, Blanchon, Marilyne, Boucekine, Mohamed, Mascaux, Celine, Barlesi, Fabrice
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2019
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - epidemiology; Carcinoma, Non-Small-Cell Lung - mortality; Costimulatory and Inhibitory T-Cell Receptors - antagonists & inhibitors; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - mortality; Female; Humans; Immuno-related adverse events; Immunotherapy - adverse effects; Immunotherapy - methods; Incidence; Lung Neoplasms - drug therapy; Male; Middle Aged; Neoplasm Staging; Nivolumab - therapeutic use; Non-small cell lung cancer; Proportional Hazards Models; Response; Retrospective Studies; Survival; Survival Analysis; Response; Immuno-related adverse events; Survival; Non-small cell lung cancer
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2018.10.002

Immune checkpoint inhibitors (ICIs) are available for first- and further lines of treatment of patients with advanced non–small-cell lung cancer (NSCLC). These treatments are associated with adverse events called immune-related adverse events (IRAEs). The incidence, diagnosis, and treatment of IRAEs are quite acknowledged; however, the link between IRAEs and the efficacy of ICIs requires further clarification. The objectives of this study were to assess the association between IRAEs incidence and severity and ICIs efficacy in patients with advanced NSCLC.
In this retrospective study, clinical, biological, treatment, and outcome data were collected from patients with advanced NSCLC who received at least 1 cycle of ICIs from April 2013 to February 2017. The primary endpoint was to assess the association of IRAEs incidence with overall survival (OS). Secondary endpoints were the association of IRAEs with progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).
Overall, 270 patients were studied. The median OS was 14 months, median PFS was 2.6 months, ORR was 13%, and DCR was 51%. OS, PFS, and ORR were significantly better for patients with IRAEs compared with patients with no IRAEs, translating to median OS not reached versus 8.21 months, respectively (hazard ratio, 0.29; 95% confidence interval [CI], 0.18-0.46; P < .001); PFS was 5.2 versus 1.97 months (hazard ratio, 0.42; 95% CI, 0.32-0.57; P < .001); and ORR was 212.9% versus 5.7% (odds ratio, 4.9; 95% CI, 2.18-11.05; P < .001).
This report presents the largest case series showing longer OS and PFS and better ORR when IRAEs occurred in a population of patients with advanced NSCLC treated with ICIs. The biological background for this phenomenon is being explored prospectively.
Immune checkpoints inhibitors (ICIs) in advanced non–small-cell lung cancer are associated with immune-related adverse events (IRAEs). We retrospectively analyzed the efficacy of ICIs in a cohort of 270 patients with the objective to assess the association of IRAEs with ICI efficacy. We found a statistically significant efficacy difference in favor of patients with IRAEs. These results could be used to determine ICI responders.