In a phase II trial (NCI Protocol 10250) reported in the Journal of Clinical Oncology, Ingham et al found that the combination of olaparib and temozolomide showed activity in previously treated patients with advanced uterine leiomyosarcoma.
Study Details
In the multicenter trial, 22 evaluable patients whose disease progressed on at least one prior line of therapy were enrolled between August 2019 and February 2020 and received temozolomide at 75 mg/m2 once daily and olaparib at 200 mg twice daily on days 1 to 7 in 21-day cycles. Overall, 13 patients (59%) had received three or more prior lines of treatment.
The primary endpoint was best objective response rate within 6 months. Treatment was to be considered promising if objective response was observed in at least 5 of 22 patients.
Responses
Median follow-up was 22 months. Objective response within 6 months was observed in five patients (23%), meeting the primary endpoint. Overall, objective responses (all partial) were observed in six patients (27%).
Stable disease was observed in an additional nine patients (41%). Median duration of response was 12.0 months (95% confidence interval [CI] = 9.5 months to not estimable). Median progression-free survival was 6.9 months (95% CI = 5.4 months to not estimable), with rates at 6, 12, and 24 months of 65%, 38%, and 22%, respectively. Median overall survival was not reached. Among 18 patients with available data, median progression-free survival was 11.2 months for 9 with homologous recombination–deficient tumors vs 5.4 months among 9 with homologous recombination–proficient tumors (P = .05).
Adverse Events
The most common grade 3 or 4 treatment-related adverse events were neutropenia (in 75% of patients), thrombocytopenia (in 32%), and anemia (in 32%); the most common nonhematologic events were nausea and diarrhea (in 4% each). Adverse events led to discontinuation of treatment in three patients, due to neutropenia, thrombocytopenia, and rash.
The investigators concluded, “Olaparib and temozolomide met the prespecified primary endpoint and provided meaningful clinical benefit in patients with advanced, pretreated uterine leiomyosarcoma.”
Matthew Ingham, MD, of the Division of Hematology and Medical Oncology, Columbia University Irving Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a Conquer Cancer Foundation of ASCO Career Development Award from the Sarcoma Foundation of America, National Cancer Institute, and others. For full disclosures of the study authors, visit ascopubs.org.
