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

Autor: 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., Coleman, Robert L.
Rok vydání: 2022
Předmět:
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
Zdroj: Gynecologic oncology, vol 164, iss 2
Aghajanian, C, Swisher, E M, Okamoto, A, Steffensen, K D, Bookman, M A, Fleming, G F, Friedlander, M, Moore, K N, Tewari, K S, O'Malley, D M, Chan, J K, Ratajczak, C, Hashiba, H, Wu, M, Dinh, M H & Coleman, R L 2022, ' 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 ', Gynecologic Oncology, vol. 164, no. 2, pp. 278-287 . https://doi.org/10.1016/j.ygyno.2021.12.012
ISSN: 0090-8258
Popis: 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.
Databáze: OpenAIRE
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