Addition of Adavosertib to Chemotherapy in Platinum-Resistant Ovarian Cancer
Posted: Tuesday, July 16, 2019
The highly selective WEE1 inhibitor adavosertib has shown activity when combined with chemotherapy, specifically carboplatin, in the treatment of patients with primary platinum-resistant ovarian cancer. However, treatment-related adverse events led to dose interruptions, and reductions for many patients. Kathleen N. Moore, MD, of the University of Oklahoma, and her colleagues, presented data from this open-label phase II study at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 5513).
“The increased but not unexpected hematologic toxicity is a challenge and could be further studied to optimize the dose schedule and supportive medications,” noted the study authors.
A total of 94 patients with recurrent platinum-resistant ovarian cancer received a combination of adavosertib plus carboplatin, gemcitabine, weekly paclitaxel, or pegylated liposomal doxorubicin in 3- or 4-week cycles. After a median treatment duration of 3 months, patients on the adavosertib and carboplatin regimen saw the greatest benefit, with an objective response rate of 67%. These patients also had a median progression-free survival of 10.1 months, compared with 5.3 months for those who received adavosertib plus paclitaxel and 1.7 months for those treated with adavosertib plus gemcitabine.
The most common grade 3 or higher adverse events for all regimens were neutropenia, thrombocytopenia, and anemia. These conditions affected 75%, 75%, and 50% of patients treated with adavosertib plus carboplatin, respectively. This cohort showed the most notable hematologic toxicity. Adverse effects led to interruptions in treatment with adavosertib (62% of patients), dose reduction (30%), and treatment discontinuation (13%).
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.
