In a population of patients newly diagnosed with ovarian cancer, researchers demonstrated that therapy is well tolerated among both patients who are BRCA-positive and -negative.
In newly diagnosed ovarian cancer, researchers demonstrated that therapy is well tolerated among patients who are both BRCA-positive and -negative. Germline BRCA mutations positively affect chemotherapy sensitivity in epithelial ovarian cancer but may also affect toxicities experienced by women with the disease, according to a study presented in conjunction with the Society for Gynecological Oncology 2020 Annual Meeting on Women’s Cancer.
The study’s goal is to evaluate how women dichotomized by BRCA status tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (BEV) on a GOG phase 1 study. According to the researchers, this study is an unplanned post hoc analysis of clinical characteristics and toxicity data based on BRCA status. Descriptive statistics and Kaplan-Meir methods were used.
The Institutional Review Board approved, multi-institutional, prospective study of women treated with IV carboplatin, paclitaxel, and BEV every 21 days (regimen 1), weekly 4 paciltaxel with carboplatin and BEV (regimen 2), or IV paclitaxel and BEV with IP cisplatin (regimen 3). BEV was continued as maintenance in all arms. Veliparib was given with cytotoxic chemotherapy either twice daily for the entirety of each cycle or on days 2 to 5 (intermittent). Primary endpoints of maximum tolerated dose (MTD) and recommended phase 2 dose were presented at ASCO 2019.
The study evaluated 424 patients, of whom 173 (40.8%) were treated on regimen 1, 128 (30.2%) on regimen 2, and 123 (29%) on regimen 3. The majority of patients were 50 to 69 years of age and Caucasian, with a performance status of 0-1. Serous histology (77.6%) was most common, followed by endometrioid (7.5%), and clear cell (5.9%). Eighty-five percent of patients in regimen 1 had grade 4-5 toxicities, 50% in regimen 2, and 45.5% in regimen 3.
Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 were BRCA positive. BRCA-positive patients, when compared with wildtype patients, experienced similar rates of anemia, febrile neutropenia, abdominal pain, nausea, vomiting, and peripheral sensory neuropathy. Median progression-free survival was not significantly different between BRCA-positive and -negative patients, although this study’s primary aim was not to evaluate outcomes.
Germline BRCA mutations positively affect chemosensitivity in epithelial ovarian cancer, but may also affect toxicities experienced by women with this disease. In this population with newly diagnosed ovarian cancer, however, the study authors showed that therapy is well-tolerated among both BRCA-positive and -negative patients.