Topotecan in patients with BRCA-associated and sporadic platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers

Abstract

ObjectiveTo evaluate the efficacy of topoisomerase I inhibitor, topotecan, in patients with recurrent BRCA+ versus BRCA− ovarian, fallopian tube, and primary peritoneal carcinomas. MethodsA single-institution retrospective analysis of platinum-resistant patients characterized for the presence or absence of known deleterious BRCA mutations. Patients received topotecan at a dose and schedule determined by their treating physician (five day or weekly). Response rate and progression-free survival (PFS) were assessed. ResultsA total of 50 patients (9 BRCA+, 41 BRCA−) were treated with topotecan. Both groups were well balanced in terms of age, stage, grade, and number of prior therapies. All patients had high-grade serous carcinoma. The clinical benefit rate in BRCA+ and BRCA− patients was 0% and 26.8% (6 PRs, 6 SDs), respectively (p=0.18). Median PFS in BRCA+ and BRCA− pts was 1.7months (95% CI: 1.0–2.8months) and 2.5months (95%CI: 1.9–2.8months), respectively (p=0.057). Median time to best response was 1.9months, and median response duration 2.6months. ConclusionsThis analysis in a heavily pretreated cohort of patients fails to support the superiority of topotecan in BRCA+ platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers. Further study of this class of agents, specifically in less heavily-pretreated patients, may still be warranted.