Pazoparib Plus Gemcitabine Enhances Anti-Tumor Activity in Patients with Platinum-Resistant Disease

The addition of pazoparib to gemcitabine enhances anti-tumor activity, particularly for patients with platinum resistant disease who derived the most benefit from combination therapy, even in the setting of receiving prior bevacizumab.

The study findings were presented in conjunction with the Society for Gynecological Oncology 2020 Annual Meeting on Women’s Cancer.

Angiogenesis inhibition is a valuable strategy for ovarian cancer (EOC), and pazopanib is a potent small molecular inhibitor of VEGF-1,-2,-3, PDGFR, c-kit, and has activity as a single agent in ovarian cancer. Researchers designed a trial to assess the benefit of adding pazopanib to gemcitabine in patients with recurrent EOC.

An open-level, randomized, multisite, phase 2 trial was conducted including patients with platinum-resistant or sensitive disease, 3 or fewer prior lines of chemotherapy, and measurable/evaluable disease. Patients were randomly assigned to weekly gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle, with or without pazopanib 800 mg QD, stratified by platinum sensitivity and number of prior lines. The primary endpoint was progression-free survival (PFS).

A total of 148 patients were enrolled 2012—2017. Median age was 63 years, 60% of participants were platinum-resistant, and surveillance was 13 months. Median PFS was 5.3 versus 2.9 months in the gemcitabine arm. The PFS effect was most pronounced in the platinum-resistant group. There was no difference in overall survival (OS). Overall recurrence rate and DCR were higher in the combination. High-grade adverse events in the combination arm included grade 3 or lower hypertension (15%), neutropenia (35%), and thrombocytopenia (12%).

The addition of pazopanib to gemcitabine enhanced anti-tumor activity; those with platinum-resistant disease derived the most benefit from combination therapy, even in the setting of receiving prior bevacizumab.

Reference

A randomized phase II evaluation of weekly gemcitabine plus pazopanib versus weekly gemcitabine alone in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. SGO Website. https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/14860. Accessed April 15, 2020.