Incremental risk of high-grade adverse events with immune checkpoint inhibitors with or without poly(adenosine diphosphate-ribose) polymerase inhibitors in first-line treatment of advanced endometrial cancer: a systematic review and meta-analysis.
Mariana Carvalho Gouveia, Helena M Obermair, Mariana Macambira Noronha et al.
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In 30 seconds
This systematic review and meta-analysis pooled six randomized phase II or III trials involving 2,995 patients with advanced or recurrent endometrial cancer receiving first-line platinum-based chemotherapy. It compared chemotherapy plus an immune checkpoint inhibitor, with or without a PARP inhibitor, against chemotherapy alone. Doublet therapy increased grade ≥3 adverse events (risk ratio 1.12, 95% confidence interval 1.02 to 1.24); triplet therapy significantly increased serious adverse events (risk ratio 2.20, 95% confidence interval 1.74 to 2.78) and grade ≥3 anemia. Neither strategy significantly increased fatal adverse events or treatment discontinuations.
Key findings
- Doublet therapy increased grade ≥3 adverse events versus chemotherapy alone (risk ratio 1.12, 95% confidence interval 1.02 to 1.24).
- Triplet therapy increased serious adverse events (risk ratio 2.20, 95% confidence interval 1.74 to 2.78).
- Triplet therapy increased grade ≥3 anemia (risk ratio 1.66, 95% confidence interval 1.14 to 2.42); doublet therapy did not.
- Neither strategy significantly increased fatal adverse events or treatment discontinuations; both increased immune-related adverse events, mostly low grade.
Why it matters
These pooled safety results help distinguish the toxicity profiles of first-line chemo-immunotherapy strategies. Adding a PARP inhibitor was associated with more serious events and severe anemia, while no significant increase in fatal events or discontinuations was observed. This supports careful consideration of the additional toxicity burden when evaluating treatment intensification, particularly given the abstract’s stated absence of a demonstrated overall survival benefit.
What to keep in mind
The analysis pooled only six randomized trials, and the triplet estimate for grade ≥3 adverse events was a nonsignificant trend (risk ratio 1.41, 95% confidence interval 0.99 to 2.01).