Journal Article

Safety evaluation of immune checkpoint inhibitors combined with chemotherapy for the treatment of small cell lung cancer: A meta‐analysis of randomized controlled trials

Galetta, Domenico, Rizzo, Alessandro, Montrone, Michele, Longo, Vito, Catino, Annamaria

2023

Overview

Background The addition of immune checkpoint inhibitors (ICIs) to chemotherapy is the new standard of care in the first‐line treatment of small cell lung cancer (SCLC). However, although the concomitant use of immunotherapy and chemotherapy can increase the antitumor efficacy, it can also increase toxicity. The present study evaluated the tolerability of immune‐based combinations in the first‐line treatment of SCLC. Methods Relevant trials were identified by searching electronic databases and conference meetings. Seven phase II and III randomized controlled trials and 3766 SCLC patients were included in the meta‐analysis (immune‐based combinations = 2133; chemotherapy = 1633). Outcomes of interest included treatment‐related adverse events (TRAEs) and the rate of discontinuation due to TRAEs. Results Immune‐based combination treatment was associated with a higher risk of grade 3–5 TRAEs (odds ratio [OR], 1.16; 95% confidence interval [CI]: 1.01–1.35). Immune‐based combinations were associated with a higher risk of TRAEs leading to discontinuation (OR, 2.30; 95% CI: 1.17–4.54). No differences were observed in grade 5 TRAEs (OR, 1.56; 95% CI: 0.93–2.63). Conclusion This meta‐analysis indicates that the addition of immunotherapy to chemotherapy in SCLC patients is associated with a higher risk of toxicity and probably of treatment discontinuation. Tools for identifying SCLC patients that would not benefit from immune‐based therapy are urgently needed. The addition of immune checkpoint inhibitors (ICIs) to chemotherapy is the new standard of care in the first‐line treatment of small cell lung cancer (SCLC). However, although the concomitant use of immunotherapy and chemotherapy can increase the antitumor efficacy, it can also increase toxicity. We performed a meta‐analysis to compare any grade treatment‐related adverse events (TRAEs), grade 3–5 TRAEs, grade 5 TRAEs, and treatment discontinuation due to TRAEs between ES‐SCLC patients treated with front‐line immune‐based combinations and those receiving chemotherapy. Seven phase II and III trials with 3766 patients were included in the analysis. Immune‐based combination treatment was associated with higher risk than chemotherapy of any grade TRAEs (odds ratio [OR], 1.63, 95% confidence interval [CI]: 1.31–2.03; p = 0.86). Unfortunately, predictive factors for toxicity have not been established for SCLC patients treated with immune‐based combinations. Tools for identifying SCLC patients that would not benefit from immune‐based therapy are urgently needed.

• Publisher: John Wiley & Sons Australia, Ltd,John Wiley & Sons, Inc,Wiley
• Subject: Cancer therapies / Chemotherapy / Chi-square test / Clinical trials / Confidence intervals / Humans / Immune checkpoint inhibitors / Immune Checkpoint Inhibitors - therapeutic use / Immunotherapy / Immunotherapy - adverse effects / Lung cancer / Lung Neoplasms - pathology / Meta-analysis / Original / Randomized Controlled Trials as Topic / safety / SCLC / Small Cell Lung Carcinoma - drug therapy / Small Cell Lung Carcinoma - etiology / Systematic review