Veliparib/Cisplatin May Improve Survival Vs Placebo in BRCA-Like Metastatic TNBC

Cisplatin plus veliparib appears to improve progression-free survival among patients with BRCA-like metastatic triple-negative breast cancer, but not in those with non–BRCA-like metastatic breast cancer.

The addition of veliparib to cisplatin yielded improvements in progression-free survival (PFS) compared with placebo and cisplatin among patients with BRCA-like metastatic triple-negative breast cancer (TNBC), according to findings from the phase 2 S1416 trial (NCT02595905). However, investigators reported that veliparib and cisplatin combination therapy did not elicit the same improvements for patients with non–BRCA-like metastatic breast cancer.

With a median follow-up of 11.1 months (interquartile range, 5.6-20.8), the median PFS among patients with germline BRCA1/2-mutated breast cancer was 6.2 months (95% CI, 2.3-9.2) with cisplatin plus veliparib and 6.4 months (95% CI, 4.3-8.2) with cisplatin plus placebo (HR, 0.79; 95% CI, 0.38-1.67; log-rank P = .54).

For patients in the BRCA-like group—those with BRCA1/2 wild-type TNBC with homologous recombination deficiency—the median PFS was 5.9 months (95% CI, 4.3-7.8) with cisplatin plus veliparib vs 4.2 months (95% CI, 2.3-5.0) with cisplatin plus placebo (HR, 0.57; 95% CI, 0.37-0.88; P =.010).

In the non-BRCA-like group, the median PFS was 4.0 months (95% CI, 2.5-4.7) with cisplatin plus veliparib vs 3.0 months (95% CI, 2.2-4.4) with cisplatin plus placebo (HR, 0.89; 95% CI, 0.60-1.33; P = .57).

Investigators conducted the randomized, double-blind, placebo-controlled phase 2 S1416 trial across 154 community and academic clinical sites across the United States. Investigators randomly assigned patients with metastatic or recurrent TNBC or germline BRCA1/2-associated metastatic or recurrent breast cancer 1:1 to receive 75 mg/m2 of intravenous cisplatin on day 1 and 300 mg of veliparib or matched placebo orally twice a day on days 1 to 14 of a 21-day cycle.

The primary end point of the trial was investigator-assessed PFS. Key secondary end points included overall survival (OS), toxicity due to treatment, objective response rate per RECIST v1.1 criteria, and clinical benefit rate.

Patients 18 years and older with histologically confirmed recurrent or metastatic TNBC or metastatic or recurrent estrogen receptor–positive or progesterone receptor–positive, HER2-negative breast cancer with deleterious germline BRCA1/2 mutations were eligible to enroll on the trial. Additional inclusion criteria included having adequate hematological, hepatic, renal, and bone marrow function; an ECOG performance status of 0 to 2; and measurable or non-measurable disease based on RECIST v1.1 criteria.

The S1416 trial included a total of 320 efficacy-evaluable patients, of whom 162 received cisplatin/veliparib and 158 received cisplatin/placebo. Investigators sorted some patients (n = 247) into 3 biomarker groups, which included BRCA1/2-mutated disease (n = 37), BRCA-like disease (n = 101), and non–BRCA-like disease (n = 109).

The median patient age in the overall population was 56 years (range, 27-80). In the cisplatin plus veliparib and cisplatin plus placebo cohorts, respectively, most patients were White (80% vs 73%), non-Hispanic (88% vs 92%), had an ECOG performance status of 0 (59% vs 56%), and had TNBC (98% vs 93%).

In the germline BRCA1/2-mutated group, the median OS was 14.2 months (95% CI, 8.1-21.0) with cisplatin plus veliparib and 15.6 months (95% CI, 12.6-21.4) with cisplatin plus placebo (HR, 1.20; 95% CI, 0.56-2.55; log-rank P = .64). No ORR for this group given the small number of patients.

In the BRCA-like group, the median OS was 14.0 months (95% CI, 10.3-20.2) with cisplatin plus veliparib vs 12.1 months (95% CI, 9.0-15.9) with cisplatin plus placebo (HR, 0.75; 95% CI, 0.48-1.17; log-rank P = .21). Additionally, the ORR was 45% (n = 21/47) vs 33% (n = 12/36) in each respective treatment cohort (P = .37).

In the non–BRCA-like group, the median OS was 10.9 months (95% CI, 8.5-13.1) with cisplatin/veliparib vs 11.1 months (95% CI, 8.2-16.1) with cisplatin/placebo (HR, 1.14; 95% CI, 0.76-1.71; log-rank P = .53). The ORR for this group was 17% (n = 8/47) vs 19% (n = 8/43) in each respective treatment cohort. Clinical benefit for this group was observed in 49% of patients in the experimental arm compared with 49% in the placebo arm.

In the cisplatin/veliparib and cisplatin/placebo cohorts, respectively, the most common grade 3 adverse effects (AEs) included neutropenia (46% vs 20%), leukopenia (27% vs 7%), anemia (23% vs 8%), and thrombocytopenia (19% vs 3%). Serious AEs related to treatment occurred in 31% and 36% of patients in each respective cohort.

Investigators reported 1 patient death in the cisplatin plus veliparib arm due to treatment-related sepsis and another patient death in the cisplatin plus placebo arm occurred due to acute kidney injury related to cisplatin plus heart failure from previous exposure to doxorubicin.


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