Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study

Gynecol Oncol. 2021 May;161(2):512-515. doi: 10.1016/j.ygyno.2021.01.037. Epub 2021 Feb 17.

Abstract

Objective: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651).

Methods: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates.

Results: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes.

Conclusions: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.

Keywords: BRCA; Epithelial ovarian cancer; Post hoc analyses; Toxicities.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / adverse effects
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / genetics*
  • Clinical Trials, Phase I as Topic
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Hematologic Diseases / chemically induced
  • Hematologic Diseases / genetics
  • Humans
  • Middle Aged
  • Multicenter Studies as Topic
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Prospective Studies

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Benzimidazoles
  • veliparib
  • Bevacizumab
  • Carboplatin
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT00989651