Phase II study of the efficacy and safety of palbociclib in patients with recurrent ovarian cancer

Objective: We describe a phase II clinical trial evaluating the safety and efficacy of the oral CDK4/6 inhibitor palbociclib in patients with recurrent ovarian cancer. Methods: Eligible patients with Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 measurable recurrent ovarian cancer were treated with oral palbociclib 125 mg daily for 21 days of a 28-day cycle. Patients with hormone receptor-positive tumors were allowed to concurrently receive an aromatase inhibitor. The primary endpoint was the biochemical response rate, determined by CA-125 response based on Gynecologic Cancer InterGroup criteria. Genomic analyses were performed using targeted next-generation sequencing. Results: The biochemical response rate among 40 patients was 8.3% (95% CI 2.2 to 23.6), and the objective response rate by CA-125 criteria and/or RECIST was 10.5% (95% CI 3.4 to 25.7). Median progression-free survival was 3.2 months. Progression-free survival rates at 6 and 12 months were 25% and 7.5%, respectively. Two patients diagnosed with recurrent low-grade serous ovarian cancer experienced long-term disease stabilization for more than 37 and 9 months, triggering a review of 12 additional low-grade serous ovarian cancer patients treated outside of the phase II trial. Exploratory tumor genomic profiling revealed potential predictors of sensitivity (CDKN2A deletion) or resistance (CCNE1 amplification or RB1 deletion), which require additional independent validation. Conclusions: Palbociclib demonstrated only modest clinical activity in unselected patients with ovarian cancer. However, cyclin-dependent kinases 4/6 inhibition showed promising clinical activity in low-grade serous ovarian cancer, warranting further study in this subtype. Further biomarker analyses may facilitate patient selection in high-grade serous ovarian cancer.