Treatment-related Adverse Events, Including Fatal Toxicities, in Patients With Extensive-stage Small-cell Lung Cancer...

The safety profile of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors when associated with chemotherapy for the treatment of patients with extensive-stage small-cell lung cancer is still not fully unraveled.

We performed a comprehensive searrch of the PubMed, Embase, and Cochrane databases for randomized controlled trials that investigated the addition of PD-1 or PD-L1 inhibitors to standard investigator choice chemotherapy. We used risk -ratios (RRs) with 95% confidence intervals (CIs) for all endpoints.

Six studies and 2,995 patients were included. At the baseline, the median age of the patients varied from 62 to 65 years, 311 (10.4%) had brain metastases, and 1,060 (35.4%) had liver metastases. PD-1/PD-L1 inhibitors were found to reduce fatal toxicities-related mortality (RR: 0.85; 95% CI: 0.80-0.91; p < 0.001; I² = 49%). The intervention group had a higher incidence of decreased appetite (RR: 1.19; 95% CI: 1.02-1.40; p = 0.03; I² = 0%), hyponatremia (RR: 1.51; 95% CI: 1.08-2.12; p = 0.02; I² = 0%), and hypothyroidism (RR: 3.14; 95% CI: 1.10-8.95; p = 0.03; I² = 81%) of any grade. Regarding adverse events of grade 3-4, there was no association of the addition of PD-1/PD-L1 inhibitors with an increased occurrence of any of the evaluated outcomes.

In this systematic review and meta-analysis, the incorporation of PD-1/PD-L1 inhibitors to chemotherapy demonstrated an excellent safety profile and to be a promising prospect for reshaping the established treatment paradigms for patients with extensive-stage small cell lung cancer.