Neoadjuvant Iniparib Plus Gemcitabine-Carboplatin Is Active in Early Triple-Negative and BRCA1/2-Mutant Breast Cancer


Key Points

  • Neoadjuvant iniparib plus gemcitabine-carboplatin was active in early triple-negative and BRCA1/2-mutant disease.
  • Higher score on an HRD-LOH assay was associated with response and could identify patients without BRCA1/2 mutation who are more likely to respond.

In the phase II PrECOG 0105 study reported in the Journal of Clinical Oncology, Telli et al found that neoadjuvant iniparib plus gemcitabine-carboplatin was active in early-stage triple-negative and BRCA1/2-mutant breast cancer. Higher score on a homologous recombination deficiency–loss of heterozygosity (HRD-LOH) tumor assay was associated with response and could identify patients without BRCA1/2 mutation who are more likely to respond.

Study Details

The study included 80 patients with stage I to IIIA (T ≥ 1 cm) triple-negative (97%) or BRCA1/2 mutant (24%) breast cancer who received six cycles of gemcitabine (1,000 mg/m2 on days 1 and 8), carboplatin (area under curve = 2 on days 1 and 8), and iniparib (5.6 mg/kg intravenously on days 1, 4, 8, and 11) every 21 days for six cycles. Patients had a median age of 48 years. Clinical stages were I in 13%, IIA in 36%, IIB in 36%, and IIIA in 15%.

The pathologic complete response rate was 36% (90% confidence interval = 27%–46%), including rates of 33% in patients with wild-type BRCA1/2, 47% in those with BRCA1/2 mutation, and 47% in those with BRCA1/2 mutation and triple-negative disease.

HRD-LOH Analysis

Mean HRD-LOH scores were higher in responders vs nonresponders (15.7 vs 12.5, P = .02). Mean HRD-LOH scores were similar in BRCA1/2-mutant vs wild-type responders but were higher in BRCA1/2 wild-type responders vs wild-type nonresponders (16.1 vs 12.3, P =.021). When an assay score of ≥ 10 was used as a cutoff for HRD, responders were significantly more likely to have scores above the cutoff among all patients (P = .0026) and among those with BRCA1/2 wild-type disease (P = .0024).

The investigators concluded: “Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted.”

Melinda L. Telli, MD, of Stanford University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by sanofi-aventis, Breast Cancer Research Foundation, National Institutes of Health, Stanford Cancer Institute, American Society of Clinical Oncology Conquer Cancer Foundation, Triple-Negative Breast Cancer Foundation, Susan G. Komen for the Cure, and Myriad Genetics. For full disclosures of the study authors, visit

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