Palbociclib in patients (pts) with ovarian cancer (OC) with CDKN2A alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with OC with alterations treated with palbociclib, an oral cyclin-dependent kinase 4/6 inhibitor, are reported. Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Tumors must not have had mutations (mut) in the gene. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Palbociclib dosing was one 125 mg capsule taken orally once daily for 21 days followed by 7 days off, until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete or partial (PR) response per RECIST v. 1.1, or stable disease (SD) of at least 16 weeks (wks) duration (SD16+). Simon 2-stage design was based on a null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage I had DC, 18 more pts were enrolled; otherwise, the cohort was closed. If ≥7 of 28 pts had DC, the null DC rate was rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and SD, and safety. DOR is defined as time from pt’s first documented OR to progressive disease (PD). Duration of SD is defined as time from tx initiation to PD. From February 2017 to April 2023, 28 pts with OC were enrolled. Table shows demographics and outcomes. Genomic profiling showed deletion (del; n=20), mut (n=4), or both mut and del (n=3). Most common co-alterations were in: (n=17), (n=15), and (n=5). 3 PRs ( del [n=3]) and 7 SD16+ ( del [n=5]; mut [n=1]; CDKN2A mut and del [n=1]) were observed for DC rate of 37% (90% CI, 24 to 100) and OR rate of 11% (95% CI, 2 to 28). The null DC rate was rejected (p=0.005). All but 1 pt with DC had serous carcinoma histology. DORs for 2 pts with PR were 26 and 60 wks. 1 pt had a PR at their final visit, decided to end study procedures, and DOR is not available. Median duration of SD for the pts with SD16+ was 30 wks (range, 16-78). 19 pts had ≥1 tx-related grade 3-4 adverse event (AE) or serious AE, including anemia, dyspnea, fatigue, leukopenia, neutropenia, and thrombocytopenia. Palbociclib showed antitumor activity in pts with OC with alterations. Additional study is warranted to confirm the efficacy of palbociclib in this pt population. .

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics