Palbociclib in Patients With Ovarian Cancer With <i>CDKN2A</i> Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Abstract

The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations. Results of a cohort of patients with ovarian cancer (OC) with <i>CDKN2A</i> alterations treated with palbociclib are reported. Eligible patients had advanced OC, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with <i>CDKN2A</i> alterations, and no remaining standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+). Simon two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. Twenty-eight patients were enrolled from February 2017 to April 2023, and all had OC with a <i>CDKN2A</i> alteration (loss [n = 21], mutation [n = 5], and loss and mutation [n = 2]). One patient was not evaluable for efficacy because of an excluded genomic finding. Three patients had a partial response and seven had SD16+ for DC and OR rates of 38% (90% CI, 25 to 100) and 11% (95% CI, 2 to 29), respectively. The null hypothesis of 15% DC rate was rejected (<i>P</i> = .004). The median PFS was 8 weeks (95% CI, 8 to 18) and the median OS was 33 weeks (95% CI, 24 to 73). Nineteen patients (68%) had at least one treatment-related grade 3-4 adverse event (AE) or serious AE including anemia, dyspnea, fatigue, leukopenia, neutropenia, and thrombocytopenia. Palbociclib met the prespecified criteria to declare a signal of activity in patients with OC and <i>CDKN2A</i> alterations.