Palbociclib achieved 38% disease control in advanced ovarian cancer patients with CDKN2A alterations

Despite an initial 80% response rate to chemotherapy, epithelial ovarian cancer (OC) remains the most lethal gynecologic malignancy, with high recurrence rates and limited options for advanced, refractory disease. Standard treatments often fail, necessitating novel targeted approaches. This study investigates palbociclib, a CDK4/6 inhibitor, in patients with OC harboring CDKN2A alterations. CDKN2A encodes p16INK4a, a natural inhibitor of CDK4/6. Loss or mutation of CDKN2A can lead to uncontrolled cell cycle progression, making CDK4/6 inhibition a rational therapeutic strategy.

This phase II basket trial, part of the Targeted Agent and Profiling Utilization Registry Study, evaluated palbociclib in patients with advanced ovarian cancer and CDKN2A alterations. Twenty-eight patients were enrolled, all with measurable disease (RECIST), ECOG PS 0-2, adequate organ function, and no remaining standard treatment options. The primary endpoint was disease control (DC), defined as objective response (OR) or stable disease (SD) lasting at least 16 weeks (SD16+). A Simon two-stage design was used, with a null DC rate of 15% versus 35% (power = 0.85, α = .10). Secondary endpoints included OR, progression-free survival (PFS), overall survival (OS), and safety. The specific dose of palbociclib was not detailed in the abstract but was a commercially available targeted agent.

Of the 28 patients enrolled, 27 were evaluable for efficacy. All patients had CDKN2A alterations (loss [n = 21], mutation [n = 5], loss and mutation [n = 2]). Three patients achieved a partial response, and seven had SD16+, leading to a disease control (DC) rate of 38% (90% CI, 25 to 100). The objective response (OR) rate was 11% (95% CI, 2 to 29).