Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer: results of exploratory analyses from the phase III BROCADE3 trial.

Abstract

BACKGROUND:

In the BROCADE3 trial, addition of the poly(ADP-ribose) polymerase inhibitor, veliparib, to carboplatin/paclitaxel improved progression-free survival (PFS) (hazard ratio 0.71, 95% confidence interval 0.57-0.88; P = 0.002) in patients with advanced human epidermal growth factor receptor 2-negative, germline BRCA1/2-mutated breast cancer. A subset of patients discontinued both carboplatin and paclitaxel before progression and continued on veliparib/placebo maintenance monotherapy until progression. Analyses in this patient subgroup are reported.

PATIENTS AND METHODS:

Patients were randomized 2 : 1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Veliparib (120 mg twice daily) or placebo was given on days -2 to 5, carboplatin (area under the curve 6 mg/ml) on day 1, and paclitaxel (80 mg/m2) on days 1, 8, and 15 of 21-day cycles. Patients who discontinued both carboplatin and paclitaxel before progression received blinded study drug monotherapy at an increased dose of 300-400 mg twice daily continuously. PFS was the primary endpoint. Exploratory analyses were carried out in the subgroup of patients who received blinded study drug as monotherapy. A time-varying Cox model including data from all patients was also used to evaluate treatment effect in the combination and monotherapy phases.

RESULTS:

A total of 136 of 337 patients randomized to veliparib plus carboplatin/paclitaxel and 58/172 patients randomized to placebo plus carboplatin/paclitaxel discontinued both carboplatin and paclitaxel before progression and continued on blinded veliparib or placebo monotherapy. In this blinded monotherapy subgroup, investigator-assessed median PFS from randomization was 25.7 months with veliparib versus 14.6 months with placebo. Hazard ratios from a time-varying Cox model favored veliparib during both combination therapy and monotherapy. Any-grade adverse events occurring in the monotherapy phase were primarily gastrointestinal. The most common grade ≥3 adverse events were neutropenia and anemia (4% each with veliparib; 5% and 2%, respectively, with placebo).

CONCLUSIONS:

Veliparib maintenance monotherapy had a tolerable safety profile and may extend PFS following combination chemotherapy.

• Authors: H S Han, B K Arun, B Kaufman, H Wildiers, M Friedlander, J P Ayoub, S L Puhalla, B A Bach, M G Kundu, N Khandelwal, D Feng, S Bhattacharya, D Maag, C K Ratajczak, V Diéras
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 33 Issue 3 Pg. 299-309 (03 2022) ISSN: 1569-8041 [Electronic] England
• PMID: 34861374 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Benzimidazoles
• veliparib
• Carboplatin
• Paclitaxel

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Benzimidazoles
• Breast Neoplasms (drug therapy, genetics)
• Carboplatin
• Female
• Germ Cells
• Humans
• Paclitaxel