Treatment-related adverse events of combination chemoimmunotherapy versus chemotherapy alone in first-line treatment for non-small cell lung cancer: a systematic review and meta-analysis of randomized clinical trials

Kazuki Takada; Shinkichi Takamori; Fumitaka Mizuki; Naoko Miura; Yasunori Shikada; Mototsugu Shimokawa

doi:10.21037/jtd-23-1532

Treatment-related adverse events of combination chemoimmunotherapy versus chemotherapy alone in first-line treatment for non-small cell lung cancer: a systematic review and meta-analysis of randomized clinical trials

J Thorac Dis. 2024 Jan 30;16(1):430-438. doi: 10.21037/jtd-23-1532. Epub 2024 Jan 10.

Authors

Kazuki Takada¹, Shinkichi Takamori², Fumitaka Mizuki³, Naoko Miura¹, Yasunori Shikada¹, Mototsugu Shimokawa^{4

5}

Affiliations

¹ Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
² Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
³ Center for Clinical Research, Yamaguchi University Hospital, Yamaguchi, Japan.
⁴ Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
⁵ Cancer Biostatistics Laboratory, Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Abstract

Background: Numerous meta-analyses have examined immunotherapy-induced adverse events (AEs) in non-small cell lung cancer (NSCLC). However, there is limited research comparing AEs from combination chemoimmunotherapy versus chemotherapy alone in the first-line NSCLC treatment, particularly regarding specific toxic symptoms and hematological toxicities associated with the addition of immune checkpoint inhibitors (ICIs).

Methods: We conducted a meta-analysis of randomized clinical trials (RCTs) comparing ICIs + non-ICIs versus non-ICIs alone as first-line therapy in NSCLC, sourced from PubMed and Scopus databases. Our objective was to assess treatment-related AEs in both regimens, focusing on identifying the more prevalent toxic symptoms and hematological toxicities with ICI treatment. We calculated the relative risks (RRs) and 95% confidence intervals (CIs), and estimated the pooled RRs and 95% CIs using common- or random-effects models.

Results: Our analysis included 10 trials with 6,008 patients. Combination chemoimmunotherapy significantly increased the risk of grade 3 or higher treatment-related AEs, treatment discontinuation, and deaths due to treatment-related AEs. Moreover, patients receiving combination chemoimmunotherapy had a significantly higher risk of certain toxic symptoms (all-grade: vomiting, diarrhea, and constipation; high-grade: fatigue and diarrhea) and pneumonitis (both all-grade and high-grade).

Conclusions: These findings offer crucial insights into the toxicity profile of combination chemoimmunotherapy, serving as a valuable resource for clinicians managing lung cancer care.

Keywords: Adverse events (AEs); chemotherapy; immunotherapy; meta-analysis; non-small cell lung cancer (NSCLC).