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Iniparib may improve benefits of gemcitabine-carboplatin in triple-negative breast cancer
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The addition of iniparib to a gemcitabine-carboplatin regimen yielded an increase in OS of nearly 5 months, according to recent study results.
The current open-label, phase 2 study was conducted to compare the efficacy and safety of gemcitabine and carboplatin with or without iniparib in 123 patients with metastatic triple-negative breast cancer.
During each 21-day period, on days 1 and 8, all patients received IV gemcitabine at 1,000 mg/m2 of body-surface area and carboplatin at a dose equivalent to an area under the concentration-time curve of 2. Patients in the IV iniparib arm received 4 mg/kg of body weight on days 1, 4, 8 and 11. However, that dose was increased to 5.6 mg/kg.
“The protocol was amended in January 2008 to increase the iniparib dose to 5.6 mg per kilogram on the basis of emerging phase 1 safety data,” the researchers wrote.
The primary endpoint of rate of clinical benefit was described as the rate of objective response — which the researchers defined as complete or partial response — plus the rate of stable disease for 6 months or more. The other primary endpoint was safety. The rate of objective response, PFS and OS were also evaluated.
There were 62 patients in the chemotherapy-alone group and 61 patients in the iniparib group. Intention-to-treat analysis results indicated that the clinical benefit was 56% in the iniparib group and 34% in the chemotherapy-alone group (P=.01). Overall response rates were 52% in the iniparib group and 32% in the chemotherapy-alone group (P=.02).
The median PFS was 5.9 months with the addition of iniparib and 3.6 months in the chemotherapy-alone group (HR for progression=0.59; P=.01). Iniparib also extended the median OS from 7.7 months to 12.3 months (HR for death=0.57; P=.01).
Adverse event profiles were similar between the two groups. Anemia, fatigue or asthenia, increased alanine aminotransferase level, leukopenia, neutropenia and thrombocytopenia were the most commonly reported grade 3 or 4 adverse events.
For more information:
- O’Shaughnessy J. N Engl J Med. 2011;doi:10.1056/NEJMoa1011418.
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It’s exciting to see a rationally designed anticancer treatment strategy such as the purported poly (adenosine diphosphate–ribose) polymerase (PARP)-inhibitor iniparib, demonstrating signs of clinical activity in early phase clinical trials.
The triple-negative breast cancer phenotype represents a further heterogeneous group of poorly understood subtypes. It may turn out that the strategy of PARP-inhibition will only be efficacious in the
BRCA-positive subset of triple-negative breast cancers. If this is the case, then novel therapeutics such as iniparib may provide benefits only to the small group of BRCA-positive breast cancers that occur every year.
– Stephen Y. Chui, MD
Assistant Professor of Medicine
Division of Hematology and Medical Oncology, Department of Medicine; Director of Breast Cancer Clinical Research (Acting), Knight Cancer Institute, Oregon Health & Science University
Disclosure: Dr. Chui reports receiving research funding from Bayer BioOncology and GlaxoSmithKline; speaking honoraria from Genentech, Amgen, GlaxoSmithKline and Sanofi-Aventis; and consulting fees from Genentech, Amgen and GlaxoSmithKline.