Impact of corticosteroids and antibiotics on efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer

Abstract

Background: Immune-checkpoint inhibitors (ICIs) are a standard-of-care in advanced non-small cell lung cancer (NSCLC). Corticosteroids are often used in symptomatic patients, but their immunosuppressive effect may reduce the efficacy of ICIs. We report our experience in NSCLC and the potential impact of on-treatment use of corticosteroids and antibiotics. Methods: Medical records of 267 patients with advanced NSCLC receiving ICIs from March 2013 to August 2018 were reviewed. Corticosteroid usage at the time of initiation or during ICIs treatment and administration of antibiotics from 3 months before the initiation of ICIs to 3 months after treatment end were collected. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survival (OS). A multivariable analysis was performed to study the influence of clinical characteristics on treatment efficacy. Results: 146 patients (55%) received corticosteroids: 43% for the treatment of irAEs and 57% for the management of baseline conditions. Prednisone (40%) and dexamethasone (35%) were the most commonly used. Median dose of prednisone equivalent was 50mg daily, 92% received ≥10mg prednisone equivalent daily. Median duration of corticosteroids was 59 days. OS was longer in the group that did not receive corticosteroids or received <10mg prednisone equivalent daily: 14.7 vs 8.3 months. No differences in PFS were observed: 4.6 vs 4.2 months. Patients with corticosteroids for baseline condition presented shorter median OS than the rest of the population: 6.5 vs 16.5 months. Multivariable analysis identified corticosteroids usage as an independent variable related to poorer outcomes. 141 patients (52.8%) received antibiotics. Quinolone (37%) and penicillin (33%) were the most commonly used. No correlation between the usage of antibiotics and efficacy of ICIs was found, with median OS of 10.2 vs 12.5 months. Conclusions: The use of≥10mg of prednisone equivalent daily was associated with poorer outcomes, especially when given for baseline condition. No correlation was found between antibiotics and survival. Corticosteroids usage may identify a population with higher volume and aggressive tumors. Prudent use of corticosteroids needs to be warranted.