Addition of iniparib, a poly(adenosine disphosphate-ribose) polymerase inhibitor to chemotherapy, increases the clinical benefit and survival in patients with triple-negative breast cancer without increasing toxicity, new research indicates.
In an open-label phase 2 study published online in the New England Journal of Medicine, Joyce O’Shaughnessy, MD, of Baylor Charles A. Sammons Cancer Center, Dallas, Texas, and colleagues compared the efficacy and safety of gemcitabine and carboplatin with or without iniparib in 123 patients with metastatic breast cancer. The primary end points were the rate of clinical benefit (ie, percentage of patients achieving a partial or complete response or stable disease for ≥6 months) and safety and tolerability of iniparib.
Addition of the PARP inhibitor to chemotherapy significantly increased the rate of clinical response from 34% to 56%. The overall response rate also increased significantly from 32% without iniparib to 52% with it. Significant improvements in median progression-free survival (from 3.6 months to 5.9 months) and median overall survival (from 7.7 months to 12.3 months) were also seen in patients receiving iniparib.
The rate of adverse events was not significantly different between the two groups. The most frequent grade 3 or 4 adverse events in both groups were neutropenia, thrombocytopenia, anemia, fatigue or asthenia, leukopenia, and increased alanine aminotransferase level.
These findings provide “proof of concept that the combination of iniparib with gemcitabine-carboplatin provides significant clinical benefit with a favorable safety profile in patients with metastatic triple-negative breast cancer,” the authors write. A phase 3 trial of iniparib plus chemotherapy in this population is now in progress.
An editorial accompanying the study says that despite limitations and unanswered questions, the findings suggest that “PARP inhibition could be a rational approach to treating triple-negative breast cancer, and the first therapy showing a survival advantage over chemotherapy alone.”