Researchers presented findings in conjunction with the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer on the phase 3 VELIA trial studying the safety of veliparib.
In the phase 3 VELIA trial studying the safety of veliparib, the resulting adverse effect (AE) frequencies were found to be generally similar among the whole patient population and biomarker-positive patient subsets, according to findings presented in conjunction with the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer.1
In the trial, patients were eligible regardless of biomarker status and were randomized to 1 of 3 treatment arms.1 They received 6 cycles (21 days/cycle) of carboplatin (AUC 6) and paclitaxel (175 mg/m2 q3w or 80 mg/m2 weekly).1 Veliparib was continuously dosed at 150 mg BID PO with carboplatin/paclitaxel and then at 300 mg BID, increasing to 400 mg BID if tolerated, for 30 additional cycles.1
Patients receiving more than or equal to 1 dose of the study drug were included in safety analyses, with researchers limiting analysis to patients randomized to carboplatin/paclitaxel plus veliparib followed by veliparib maintenance.1 AEs in patients randomized to carboplatin/paclitaxel plus veliparib followed by veliparib maintenance were reported for the whole patient population, as well as for the BRCA-mutated (BRCAm) and homologous recombination deficiency (HRD) patient subsets.1
During the entire treatment period that combined chemotherapy and maintenance, grade 2 to 4 nonhematologic AEs were predominantly gastrointestinal.1 Grade 3 to 4 hematologic AEs included neutropenia and anemia in more than one-third of patients.1
The frequency of common AEs was generally comparable in the whole population and the BRCAm and HRD patient subsets; the frequency of AEs leading to dose reduction was also comparable.1 In the whole population, the prevalence of all-grade neutropenia, anemia, thrombocytopenia, and nausea decreased substantially from cycles 7 to 9 to cycles 10 to 12 (in which cycle 7 was the first cycle of monotherapy maintenance).1
The researchers concluded that the use of veliparib, when dosed concurrently with carboplatin/paclitaxel and continued as maintenance monotherapy, resulted in a significant improvement in progression-free survival compared with carboplatin/paclitaxel alone in patients who were newly diagnosed with stage 3 to 4 high-grade serous ovarian, fallopian tube, and peritoneal cancer.1
Based on these results, researchers also hypothesized that although DNA repair deficiencies may improve response to PARP inhibition, they may cause patients with BRCAm or HRD tumors to be more sensitive to treatment-related toxicities.1