title: Topotecan in patients with BRCA-associated and sporadic platinum-resistant ovarian, fallopian tube, and primary peritoneal cancers.
abstract: 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.
authors.affiliation: Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Hyman
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Angela G
authors.initials: AG
authors.lastname: Arnold
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Grisham
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: Noah D
authors.initials: ND
authors.lastname: Kauff
authors.forename: David
authors.initials: D
authors.lastname: Spriggs
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010984:Platinum / Q000627:therapeutic use; D012189:Retrospective Studies; D059004:Topoisomerase I Inhibitors / Q000627:therapeutic use*; D019772:Topotecan / Q000627:therapeutic use*
chemical_list: D059004:Topoisomerase I Inhibitors; D010984:Platinum; D019772:Topotecan