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

Abstract

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.

Treatment-related adverse events of immune checkpoint inhibitors in clinical trials: a systematic review and meta-analysis

“…Mei et al (31) identified 33 RCTs and found that camrelizumab or avelumab combined with chemotherapy showed higher incidences of all-grade AEs, whereas durvalumab and sintilimab could be considered relatively safe PD-L1 and PD-1 inhibitors. Longo et al (16) identified seven RCTs and found that ICI-based combined treatment was associated with a high risk of grade 3-5 trAEs in patients with small cell lung cancer. Hao et al (32) showed that ICIs + nab-paclitaxel/paclitaxel were associated with a lower risk of irAEs than that seen with ICI monotherapy.…”

“…Several systematic reviews and meta-analyses have investigated ICI adverse effects on cancer at specific sites and found that the use of ICIs could increase the risk of toxicity and treatment discontinuation (13)(14)(15)(16)(17). The increased risk of AEs is a challenge in the development of novel ICIs, especially for combined treatments in clinical practice (18).…”

Lethal Immune-Related Pneumonitis after Durvalumab Therapy for Small Cell Lung Cancer: A First Case in China

“…Small cell lung cancer (SCLC) accounts for approximately 14% of all lung cancers [ 1 , 2 ]. Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have become the new standard of care for the first-line treatment of extensive-stage SCLC, such as durvalumab plus platinum and etoposide [ 3 ].…”

Efficacy of First-Line Immunotherapy Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients With Different Brain Metastases Status: A Systematic Review and Meta-Analysis

“…Given the potential incidence of adverse events associated with immunotherapy [15], it becomes imperative to determine whether ES-SCLC patients with brain metastases can derive maximal benefit from this treatment approach. The existing inconsistencies in the literature underscore the necessity for a systematic review aimed at evaluating the treatment outcomes of first-line immunotherapy combined with chemotherapy in ES-SCLC patients with varying brain metastasis statuses.…”