Evolving Maintenance Approaches: Clinical Trial Updates in Ovarian Cancer

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Frontline immunotherapy research in ovarian cancer shows promising signals through key studies including FIRST and KEYNOTE trials. The FIRST study demonstrates improved progression-free survival when adding dostarlimab to niraparib maintenance therapy regardless of homologous recombination deficiency (HRD) status, while KEYNOTE-L reveals benefits from combining pembrolizumab with olaparib in frontline treatment. Notably, pembrolizumab alone showed no benefit, highlighting the importance of PARP inhibitor and immunotherapy combinations.

The biological rationale for combining PARP inhibitors with immunotherapy centers on creating immunologically “hot” tumors from “cold” ones. PARP inhibitors induce DNA double-strand breaks, leading to viral mimicry and enhanced immune activation within the tumor microenvironment. Subset analyses suggest particular benefit in HRD-proficient, bevacizumab-negative patients, though these findings require validation in larger patient populations.

Current evidence does not support routine frontline immunotherapy use in ovarian cancer, but emerging data suggests specific patient subgroups may benefit significantly. The complexity of study designs with multiple biomarker subgroups and treatment arms makes interpretation challenging, requiring careful analysis of individual study components. While not yet practice-changing, these developments represent important progress toward identifying patients with ovarian cancer most likely to benefit from immunotherapy combinations in the frontline setting.