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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.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2022 Feb; Vol. 164 (2), pp. 278-287. Date of Electronic Publication: 2021 Dec 18. - Publication Year :
- 2022
-
Abstract
- Objective: In 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.<br />Methods: Women 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.<br />Results: 1132 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 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCAwt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, 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.<br />Conclusions: DD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.<br />Competing Interests: Declaration of competing interest None.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Carboplatin administration & dosage
Carcinoma, Ovarian Epithelial genetics
Carcinoma, Ovarian Epithelial pathology
Drug Administration Schedule
Female
Genes, BRCA1
Genes, BRCA2
Germ-Line Mutation
Hereditary Breast and Ovarian Cancer Syndrome genetics
Hereditary Breast and Ovarian Cancer Syndrome pathology
Humans
Induction Chemotherapy
Maintenance Chemotherapy
Middle Aged
Neoplasms, Cystic, Mucinous, and Serous genetics
Neoplasms, Cystic, Mucinous, and Serous pathology
Ovarian Neoplasms genetics
Ovarian Neoplasms pathology
Progression-Free Survival
Young Adult
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Benzimidazoles therapeutic use
Carcinoma, Ovarian Epithelial drug therapy
Hereditary Breast and Ovarian Cancer Syndrome drug therapy
Neoplasms, Cystic, Mucinous, and Serous drug therapy
Ovarian Neoplasms drug therapy
Paclitaxel administration & dosage
Poly(ADP-ribose) Polymerase Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6859
- Volume :
- 164
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 34930617
- Full Text :
- https://doi.org/10.1016/j.ygyno.2021.12.012