The WEE1 tyrosine kinase inhibitor AZD1775 enhanced carboplatin’s antitumor activity in a phase II proof-of-concept trial of refractory or resistant TP53-mediated ovarian cancer, according to a report in the Journal of Clinical Oncology.
The manufacturer-sponsored open-label nonrandomized trial involved 23 women (median age, 58 years; range, 25-74 years) who had epithelial ovarian cancer and TP53 mutations and whose disease didn’t respond to or recurred after first-line platinum plus paclitaxel therapy. All the participants also underwent either primary or interval debulking surgery, said Suzanne Leijen, MD, PhD, of The Netherlands Cancer Institute, Amsterdam, and her associates.
The patients took 225 mg AZD1775 orally twice a day for 3 days along with IV carboplatin in 21-day cycles, until the cancer progressed. The primary outcome measure, overall response rate, was 43% in the 21 evaluable patients. After two treatment cycles, one patient had a complete response, eight had a partial response, seven had stable disease, and five had progressive disease.
“This response rate exceeds the effect that could be expected with second-line single-agent treatment options, including paclitaxel, pegylated liposomal doxorubicin, bevacizumab, and topotecan, which have reported response rates of 11%-21%,” the investigators said (J Clin Oncol. 2016 Oct. 31. doi: 10.1200/JCO.2016.67.5942).
The median progression-free survival was 5.3 months and median overall survival was 12.6 months. One patient showed a partial response for 31 months and another showed a complete response for 42 months, and both continue to receive the treatment.
AZD1775 plus carboplatin “was generally well tolerated and demonstrated manageable toxicity,” including nausea, vomiting, diarrhea, fatigue, bone marrow suppression, thrombocytopenia, and neutropenia.
This study was supported by Merck, which was involved in the data analysis and interpretation. Dr. Leijen reported having no relevant financial disclosures; her associates reported ties to Merck, AstraZeneca, Roche, Novartis, Advaxis, and Modra Pharmaceuticals.
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