Adding immunotherapy to chemotherapy may increase the risk of toxicity and likelihood of treatment discontinuation in patients with small-cell lung cancer (SCLC), according to a meta-analysis published in Thoracic Cancer.

The meta-analysis included 6 phase 3 randomized controlled trials (RCTs) and 1 phase 2 RCT. The trials encompassed 3766 SCLC patients, including 2133 who received immunotherapy plus chemotherapy and 1633 who received chemotherapy alone.

Immunotherapies studied included serplulimab, adebrelimab, durvalumab, tremelimumab, atezolizumab, pembrolizumab, and ipilimumab. Chemotherapy consisted of a platinum agent in combination with etoposide or paclitaxel.

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There was a higher risk of any treatment-related adverse events (TRAEs) with immunotherapy-based treatment than with chemotherapy alone (odds ratio [OR], 1.63; 95% CI, 1.31-20.03). There was also a higher risk of grade 3-5 TRAEs with immunotherapy-based treatment than with chemotherapy alone (OR, 1.16; 95% CI, 1.01-1.35). 

Immunotherapy-based combinations were associated with an increased risk of TRAEs leading to discontinuation as well (OR, 2.30; 95% CI, 1.17-4.54). However, the researchers noted that this finding “should be interpreted with caution” because the studies used different immunotherapies and the trial populations were heterogeneous.

“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,” the researchers wrote. “Tools for identifying SCLC patients that would not benefit from immune-based therapy are urgently needed.”


Longo V, Rizzo A, Catino A, Montrone M, Galetta D. Safety evaluation of immune checkpoint inhibitors combined with chemotherapy for the treatment of small cell lung cancer: A meta-analysis of randomized controlled trials. Thorac Cancer. Published online March 3, 2023. doi:10.1111/1759-7714.14842