The discussant of the iniparib data (abstract 1007), Lisa A. Carey, MD, Medical Director of the University of North Carolina Breast Center, noted that the phase II results provoked “great enthusiasm and high expectations from doctors and patients” but the primary statistical endpoint was not met. “There was a numerical signal in favor of iniparib, but the effect size was small,” she noted. “Even if it is real, is a 1-month advantage in progression-free survival and less than 1 month in overall survival clinically meaningful?”
The exploratory analysis, in which adjustment for baseline differences in disease-free interval marginally improved the P value, is “interesting and hypothesis-generating,” she added.
While the two trials and their populations were quite similar, baseline differences may have figured into the inconsistent results—for example, the proportions of BRCA-mutated tumors and atypical molecular profiles within the groups are unknown, she said. “Triple-negative eligibility enriches for subtypes of biologic interest but will misclassify some,” she pointed out. “However, we have no reason to think this happened in a differential manner across the two trials,” she added. Importantly, gemcitabine/carboplatin is probably not the preferred backbone regimen for triple-negative breast cancer.
“We have learned from this study that the role and mechanism of iniparib is still a work in progress, and clinical activity is less than predicted; that triple-negative phenotype alone is unlikely to be an adequate selection strategy for PARP inhibition; and that gemcitabine/carboplatin as a chemotherapy backbone has modest activity,” she said.
While further study of this interesting and rather nontoxic drug is underway, as is a search for relevant biologic pathways within triple-negative breast cancer, conventional chemotherapy remains the mainstay of treatment, according to Dr. Carey. ■
Financial Disclosure: Dr. Carey has served as an uncompensated consultant or advisor for Genentech, GlaxoSmithKline, Novartis, Pfizer, sanofi-aventis, Schering-Plough, and Wyeth.
As reported in the March 15 issue of The ASCO Post, a phase III trial of the novel agent iniparib failed to demonstrate a significant improvement in survival for women with metastatic triple-negative breast cancer. The “top-line” results were communicated in the spring via press releases from...