The Wee1 inhibitor adavosertib, given alone or in combination with olaparib, was effective in patients with poly (ADP-ribose) polymerase (PARP)-resistant ovarian cancer in the phase II EFFORT trial presented by Shannon Neville Westin, MD, of The University of Texas MD Anderson Cancer Center.1
EFFORT was a randomized noncomparative study of oral adavosertib with or without olaparib in women with PARP-resistant ovarian cancer.
Shannon Neville Westin, MD
“Arguably, the majority of patients with ovarian cancer will receive a PARP inhibitor at some point during their cancer therapy, whether that be in the front-line setting, as second-line maintenance, or as a treatment strategy in recurrence,” said Dr. Westin. “With the increased use of PARP inhibitors, we are seeing increased incidence of resistance to PARP inhibitors, and this can occur through multiple different mechanisms.”
For the phase II EFFORT study, investigators randomly assigned 80 women with disease progression after PARP inhibitor therapy to receive either adavosertib alone or in combination with olaparib. Treatment with adavosertib alone led to responses in 23% of patients; in combination with olaparib, responses were observed in 29%. Median duration of response was 5.5 months and 6.4 months, respectively.
With adavosertib alone, a 63% clinical benefit rate was seen, and this benefit occurred irrespective of BRCA mutation status. Similarly, in the adavosertib/olaparib arm, despite a median of four prior lines of therapy, patients were able to stay on study for over 60 days, achieving an “incredibly impressive” 89% clinical benefit, Dr. Westin noted, adding that “deep and durable responses are possible” with or without olaparib. Toxicities were generally manageable with supportive care and dose interruptions or reduction.
DISCLOSURE: Dr. Westin has served in a consulting or advisory role for Agenus, AstraZeneca, Bioascend, Casdin Capital, Circulogene Theranostics, Clovis Oncology, Curio Science LLC, Eisai, Genentech, Gerson Lehrman Group, GlaxoSmithKline, Medscape, Merck, Novartis, OncLive, Pfizer, Roche, Targeted Oncology, Tesaro, Vaniam Group, Watermark Research Partners, and Zentalis; has received research funding from ArQule, AstraZeneca, Bayer, Clovis Oncology, Cotinga Pharmaceuticals, Novartis, Roche/Genentech, and Tesaro; has an immediate family member who has received research funding from Celgene, Karyopharm Therapeutics, and Kite Pharma; and has received institutional research funding from Bio-Path, GOG Foundation, and Mereo BioPharma.
1. Westin SN, Coleman RL, Fellman BM, et al: 2021 ASCO Annual Meeting. Abstract 5505. Presented June 7, 2021.