WEE1 Inhibitor Adavosertib Plus Gemcitabine in High-Grade Serous Ovarian Cancer
Posted: Thursday, February 18, 2021
According to a phase II randomized controlled trial published in The Lancet, the WEE1 inhibitor adavosertib plus gemcitabine improved progression-free survival and overall survival in patients with high-grade serous ovarian cancer, compared with placebo plus gemcitabine. Although this combination has demonstrated preclinical synergy and activity in early-phase clinical trials, this is reportedly the first trial to show a benefit in this patient population.
Amit M. Oza, MD, of the Princess Margaret Cancer Centre, Toronto, and colleagues conducted this double-blind trial of women with platinum-refractory or platinum-refractory recurrent ovarian cancer in the United States and Canada. More than 120 patients, with a median age of 62, were randomly assigned to receive intravenous gemcitabine (1,000 mg/m2 on days 1, 8, and 15) with either oral adavosertib (175 mg) or an identical placebo once daily on days 1, 2, 8, 9, 15, and 16, in 28-day cycles until disease progression or unacceptable toxicity.
The study authors reported that progression-free survival was longer in patients treated with adavosertib plus gemcitabine (median, 4.6 months) compared with placebo plus gemcitabine (median, 3.0 months). Median overall survival was 11.4 months for adavosertib plus gemcitabine compared with 7.2 months for placebo plus gemcitabine. In both groups, the most common toxicities were hematologic, including neutropenia (62% of those given adavosertib vs. 30% of those given placebo) and thrombocytopenia (31% vs. 6%), and fatigue.
“Building on the biology of high-grade serous ovarian cancer, a TP53-mutated tumor type with high replication stress, these results of a WEE1 inhibitor combined with gemcitabine highlight the importance of DNA damage response targeted agents in this disease. This therapeutic approach might be applicable to additional tumor types with high replication stress. Larger confirmatory studies are required,” the authors commented.
Disclosure: Full authors’ disclosures are available at thelancet.com