1. Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer – an ancillary data analysis of the VELIA trial
- Author
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Aghajanian, Carol, Swisher, Elizabeth M., Okamoto, Aikou, Steffensen, Karina Dahl, Bookman, Michael A., Fleming, Gini F., Friedlander, Michael, Moore, Kathleen N., Tewari, Krishnansu S., O'Malley, David M., Chan, John K., Ratajczak, Christine, Hashiba, Hideyuki, Wu, Meijing, Dinh, Minh H., and Coleman, Robert L.
- Subjects
Genes, BRCA2 ,Genes, BRCA1 ,Carcinoma, Ovarian Epithelial ,Carboplatin ,Neoplasms ,Ovarian Epithelial ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Mucinous ,Cancer ,Aged, 80 and over ,Ovarian Neoplasms ,Obstetrics and Gynecology ,Induction Chemotherapy ,Middle Aged ,Progression-Free Survival ,Oncology ,6.1 Pharmaceuticals ,Hereditary Breast and Ovarian Cancer Syndrome ,Female ,Patient Safety ,Adult ,Homologous recombination de ficiency ,Paclitaxel ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,Poly(ADP-ribose) Polymerase Inhibitors ,Drug Administration Schedule ,Maintenance Chemotherapy ,Paediatrics and Reproductive Medicine ,Cystic ,Young Adult ,Rare Diseases ,Ovarian cancer ,gBRCA ,Clinical Research ,Humans ,Oncology & Carcinogenesis ,Germ-Line Mutation ,Aged ,Dose-dense paclitaxel ,and Serous ,Carcinoma ,Veliparib ,Evaluation of treatments and therapeutic interventions ,BRCA1 ,g BRCA ,BRCA2 ,PARP inhibitor ,Genes ,Benzimidazoles ,Homologous recombination deficiency ,Neoplasms, Cystic, Mucinous, and Serous - Abstract
ObjectiveIn the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status.MethodsWomen with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status.Results1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n=586) versus Q3W (n=546) paclitaxel (ITT: 20.5 vs 15.7months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8months, HR 0.64; BRCAwt: 18.0 vs 12.9months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between gBRCAm (n=211) and gBRCAwt (n=902) subgroups.ConclusionsDD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.
- Published
- 2022