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Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105. | LitMetric

Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation-Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105.

J Clin Oncol

Melinda L. Telli, Kristin C. Jensen, Shaveta Vinayak, Allison W. Kurian, Jafi A. Lipson, Patrick J. Flaherty, Elizabeth A. Schackmann, Irene L. Wapnir, Robert W. Carlson, Pei-Jen Chang, and James M. Ford, Stanford University School of Medicine, Stanford; Bobbie Head, Marin Specialty Care, Greenbrae, CA; Kirsten Timms, Victor Abkevich, Julia E. Reid, and Anne-Renee Hartman, Myriad Genetics, Salt Lake City, UT; Joseph A. Sparano, Albert Einstein College of Medicine, New York, NY; Lori J. Goldstein, Fox Chase Cancer Center, Philadelphia, PA; Barbara Haley, University of Texas Southwestern Medical Center, Dallas, TX; Shaker R. Dakhil, Cancer Center of Kansas, Wichita, KS; and Judith Manola, Dana-Farber Cancer Institute, Boston, MA.

Published: June 2015

AI Article Synopsis

  • - The study evaluated the effectiveness and safety of iniparib combined with gemcitabine and carboplatin in treating early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.
  • - Involved 80 patients, with a 36% overall pathologic complete response rate, indicating a significant impact of the treatment.
  • - The results revealed that patients with higher homologous recombination deficiency (HRD-LOH) scores had better responses, suggesting HRD-LOH could help identify effective treatment candidates even among those without BRCA mutations.

Article Abstract

Purpose: This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation-associated breast cancer.

Patients And Methods: This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor-negative (≤ 5%), progesterone receptor-negative (≤ 5%), and human epidermal growth factor receptor 2-negative or BRCA1/2 mutation-associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m(2) intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies.

Results: Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021).

Conclusion: 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451172PMC
http://dx.doi.org/10.1200/JCO.2014.57.0085DOI Listing

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