Topotecan in patients with BRCA-associated and sporadic platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers.
OBJECTIVE:To evaluate the efficacy of topoisomerase I inhibitor, topotecan, in patients with recurrent BRCA+ versus BRCA- ovarian, fallopian tube, and primary peritoneal carcinomas. METHODS:A 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. RESULTS:A 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 1.7 months (95% CI: 1.0-2.8 months) and 2.5 months (95%CI: 1.9-2.8 months), respectively (p=0.057). Median time to best response was 1.9 months, and median response duration 2.6 months. CONCLUSIONS:This 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.
Hyman, DM; Zhou, Q; Arnold, AG; Grisham, RN; Iasonos, A; Kauff, ND; Spriggs, D
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