Combination of Iniparib, Gemzar®, and Carboplatin for TNBC

by Dr. C.H. Weaver M.D. 9/1/2016

The combination of iniparib, Gemzar® (gemcitabine), and carboplatin appears promising in the initial treatment of patients with early-stage triple-negative breast cancer with a BRCA1/2 mutation. In addition, researchers have found ways to identify patients without a BRCA mutation who are likely to benefit. These findings were published in the Journal of Clinical Oncology.

Breast cancers that are not stimulated to grow from exposure to estrogen or progesterone and are HER2 (human epidermal growth factor receptor)-negative are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options.

Researchers recently carried out a study to assess the efficacy and safety of iniparib, Gemzar, and carboplatin in patients with early-stage triple-negative breast cancer. About a quarter of these patients (24%) had tested positive for a BRCA1/2 mutation. The researchers also looked at ways to predict which patients were most likely to respond to the treatment combination regardless of BRCA status.

Eighty patients participated in the study. They received a combination of iniparib, Gemzar, and carboplatin as neoadjuvant treatment­­­; the first step in the therapy process to shrink the tumor before the main treatment. Patients received the drugs every 21 days for six cycles.

Of the 80 patients in the study, 36% had what the researchers considered a “pathologic complete response.” This meant that patients had no invasive cancer in their breasts or under their arms (armpit). Patients with a BRCA mutation were most likely to respond to treatment.

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The researchers also used tests to detect tumor response the treatments used in the study—tests for a response known as homologous recombination deficiency (HRD) and loss of heterozygosity (LOH). The HRD-LOH score shows the inability of cancer cells to repair DNA damage caused by treatment, or how sensitive the cancer is to drugs used.

In this study, HRD-LOH scores were higher in the patients who were considered responders—those whose tumors shrank with treatment. The HRD-LOH score appeared to predict tumor response independent of BRCA status. This means that of patients without a BRCA mutation, those with a high HRD-LOH tended to respond to the treatment combination. As a result, HRD-LOH scores may be used to help doctors choose patients most likely to benefit from the combination of iniparib, Gemzar, and carboplatin, regardless of BRCA status.

According to these findings, initial treatment with the combination of iniparib, Gemzar, and carboplatin appears active in patients with early-stage BRCA-positive triple-negative breast cancer. In addition, patients with a higher HRD-LOH score were more likely to respond. The researchers concluded that further study is needed to confirm these findings.

Reference: Telli ML, Jensen KC, Vinayak S, et al. 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. Journal of Clinical Oncology. 2015 April 6. pii: JCO.2014.57.0085.

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