Veliparib plus cisplatin improves progression-free survival (PFS) over cisplatin alone in patients with BRCA-like triple-negative breast cancer (TNBC), according to research published in The Lancet Oncology.

The study also showed that veliparib did not improve PFS for patients with non-BRCA-like TNBC or those with BRCA1/2-mutated breast cancer. Veliparib did not improve overall survival (OS) for any of the patient groups.

This phase 2 trial (ClinicalTrials.gov Identifier: NCT02595905) included 320 patients with metastatic or recurrent TNBC or germline BRCA1/2-associated metastatic or recurrent breast cancer. 


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All patients received cisplatin at 75 mg/m2 on day 1 of each 21-day cycle. They were randomly assigned to receive placebo (n=158) or veliparib at 300 mg (n=162) twice daily on days 1-14. Treatment was continued until disease progression, intolerable toxicity, or study withdrawal. 

The median age at baseline was 56 years in both treatment arms (overall range, 26-80 years). All patients in the veliparib arm and 99% in the placebo arm were women. Most patients were White (80% and 73%, respectively), had TNBC (98% and 93%, respectively), and had visceral disease (65% and 68%, respectively).

The study’s primary outcome was investigator-assessed PFS. At a median follow-up of 11.1 months, PFS events occurred in 87% of patients in the veliparib arm and 95% of those in the placebo arm. 

Veliparib was associated with improved PFS in the setting of BRCA-like TNBC. The median PFS was 5.9 months in the veliparib arm and 4.2 months in the placebo arm (hazard ratio [HR], 0.57; 95% CI, 0.37-0.88; P =.010). 

There was no improvement in PFS with veliparib in the setting of BRCA1/2-mutated breast cancer. In this group, the median PFS was 6.2 months in the veliparib arm and 6.4 months in the placebo arm (HR, 0.79; 95% CI, 0.38-1.67; P =.54). 

Likewise, there was no improvement in PFS with veliparib for patients with non-BRCA-like TNBC. In this group, the median PFS was 4.0 months in the veliparib arm and 3.0 months in the placebo arm (HR, 0.89; 95% CI, 0.60-1.33; P =.57). 

Veliparib did not improve OS compared with placebo for any of the subgroups, including:

  • BRCA1/2-mutated breast cancer (median OS, 14.2 months vs 15.6 months; HR, 1.20; 95% CI, 0.56-2.55; P =.64)
  • Non-BRCA-like TNBC (median OS, 10.9 months vs 11.1 months; HR, 1.14; 95% CI, 0.76-1.71; P =.53)
  • BRCA-like TNBC (median OS, 14.0 months vs 12.1 months; HR, 0.75; 95% CI, 0.48-1.17; P =.21).

Grade 1-2 adverse events (AEs) occurred in 24% of patients in the veliparib arm and 43% of those in the placebo arm. Grade 3 AEs occurred in 55% and 46%, respectively. Grade 4 AEs occurred in 19% and 5%, respectively. Fatal AEs occurred in 1% of patients in each arm. 

The most common grade 4 AEs in the veliparib arm were neutrophil count decrease (15%), platelet count decrease (4%), and white blood cell count decrease (3%).

Based on these results, the researchers concluded that PARP inhibitors combined with platinum-based chemotherapy should be explored further in BRCA-like TNBC.

Disclosures: This research was partly supported by AbbVie and Myriad Genetics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference

Rodler E, Sharma P, Barlow WE, et al. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. Published online January 6, 2023. doi:10.1016/S1470-2045(22)00739-2