Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial

Abstract

Objective: The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1.

Methods: PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint).

Results: Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11-1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16-2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab.

Conclusion: Results in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT02477644.

Keywords: BRCA Mutation; Bevacizumab; Homologous Recombination Deficiency; Newly Diagnosed Advanced Ovarian Cancer; Olaparib; PAOLA-1.

Conflict of interest statement

Professor Keiichi Fujiwara reports receiving consulting fees and grant support from Pfizer, Eisai, Merck Sharp & Dohme, Taiho, Zeria, Chugai Pharmaceutical, Genmab, and Takeda Pharmaceutical Company, receiving grant support from Immunogen, Oncotherapy, and Regeneron, and receiving consulting fees from Novartis, Kyowa Hakko Kirin, Daiichi Sankyo, Mochida Pharmaceutical, and NanoCarrier; Dr Toyomi Satoh reports receiving consulting fees from AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Kyowa Kirin, Eisai, Tsumura, Nippon Kayaku, Mochida Pharmaceutical, Bayer Yakuhin, ASKA Pharmaceutical, Bristol-Myers Squibb, Taiho Pharmaceutical, Takeda Pharmaceutical Company, Kaken Pharmaceutical, Nobelpharma, and Ono Pharmaceutical; Dr Kan Yonemori reports receiving lecture fees and advisory fees from Takeda Pharmaceutical Company and Esai, receiving lecture fees from AstraZeneca, Pfizer, and Daiichi Sankyo, and advisory fees from Chugai Pharmaceutical, Ono Pharmaceutical, and Novartis; Dr Shogi Nagao reports receiving consulting fees and grant support from Takeda Pharmaceutical Company, consulting fees from Chugai Pharmaceutical, AstraZeneca, Asahi Kasei Medical, and Mochida Pharmaceutical, and grant support from AbbVie, Clovis Oncology, Pfizer, Toray, Tosoh, and Preferred Networks; Dr Philipp Harter reports receiving consulting fees and grant support AstraZeneca, Roche, Tesaro, and GlaxoSmithKline, consulting fees from Sotio, Zai Lab, Merck Sharp & Dohme, Clovis Oncology, and Immunogen, and grant support from Boehringer Ingelheim, Medac, Genmab, the European Union, Deutsche Krebshilfe, and Deutsche Forschungsgemeinschaft; Dr Isabel Palacio Vazquez reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Novartis, GlaxoSmithKline, and Bristol-Myers Squibb, travel fees from Novartis, GlaxoSmithKline, and Roche, and advisory board fees from AstraZeneca, Bristol, GSK, and Clovis Oncology; Tomoko Fujita reports being employed by AstraZeneca and being a shareholder of AstraZeneca; Philip Rowe reports being employed by AstraZeneca; Professor Eric Pujade-Lauraine reports receiving consulting and other non-financial support from AstraZeneca, Roche, and Tesaro, consulting fees from Clovis Oncology, Incyte, and Pfizer, and holds the role as chairperson in ARCAGY Research; Professor Isabelle Ray-Coquard reports receiving consulting fees, grant and travel support from AstraZeneca and Roche, consulting fees and travel support from GlaxoSmithKline, consulting fees from Clovis Oncology, PharmaMar, Mersana Therapeutics, Deciphera Pharmaceutical, Amgen, and Chugai Pharmaceutical, grant support from Bristol Myers Squibb, and consulting fees and grant support from Merck Sharp & Dohme; Dr Hiroyuki Fujiwara, Dr Hiroyuki Yoshida, Dr Takashi Matsumoto, Dr Hiroaki Kobayashi, Dr Hugues Bourgeois, Dr Anna Maria Mosconi, and Dr Alexander Reinthaller report no potential conflict of interest relevant to this article.

Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.

Figures

Fig. 1. Patient disposition for the PAOLA-1 Japan subset.

Fig. 2. Kaplan-Meier estimate of investigator assessed progression-free survival in the Japan subset.