PARP Inhibitor Improves Survival in Triple-Negative Breast Cancer

MILAN—The investigative poly (ADPribose) polymerase (PARP) inhibitor iniparib (BSI-021) im proved not only progression-free survival (PFS) but also overall survival (OS) in the final analysis of a randomized phase 2 study, presented at the 35th European Society for Medical Oncology Congress by Joyce O’Shaughnessy, MD, of US Oncology and Baylor Sammons Cancer Center, Houston.

Co-investigator John E. Pippen, MD, of Texas Oncology, Dallas, said in a press briefing, “These tumors are very troublesome, as they are associated with high rates of symptomatic visceral and brain metastases. Progressionfree survival is short, and median survival is only about 13 months. There are limited treatment options.”

One emerging option seems to be agents that inhibit PARP, a key enzyme in cell proliferation and DNA repair that is upregulated in triplenegative tumors. Iniparib and olaparib are the first two agents in this class and “may prove valuable in triplenegative breast cancer as well as other types of cancers,” Pippen said.

The open-label study included 123 patients who received iniparib (5.6 mg/kg) plus gemcitabine (1000 mg/m2) and carboplatin (AUC = 2) every 3 weeks, or gemcitabine/carboplatin alone. Patients in the iniparib arm not only had a longer time to progression but also a longer survival time than patients receiving only standard chemotherapy.

Median OS was 12.2 months with the combination, compared with 7.7 months without iniparib, which was a 43% reduction in risk (P = .014). Median PFS was 5.9 versus 3.6 months (P = .012), respectively. Objective responses were observed in 52.5% of those in the combination arm compared with 32.3% of those receiving standard chemotherapy (P = .023), and the clinical benefit rate was 55.7% compared with 33.9% (P = .015), respectively, O’Shaughnessy reported.

“The magnitude of survival advantage is unusual in breast cancer and in metastatic tumors in general,” she offered. “This may be the first therapy available specifically for these patients with few options.”

Most patients had three metastatic sites of disease, and 60% had received no prior treatment for them.

Adverse events were similar between the arms. Grade 3/4 toxicities, which were primarily hematologic, were seen in 81% of patients receiving the combination versus 86% of those receiving standard chemotherapy. Serious events occurred in 29% and 28% of patients, respectively. Fewer patients discontinued treatment because of toxicity in the iniparib arm.

Commenting on the findings, Angelo Di Leo, MD, head of Sandro Pitigliani Medical Oncology Unit at the Hospital of Prato, Italy, said, “Triple-negative breast cancer accounts for about 15% of all breast cancers, and there is a desperate need to identify effective agents for these patients. This trial suggests a clear superiority of combining chemotherapy with iniparib over chemotherapy alone. Such a clear superiority is not usually observed in a trial where only 123 patients have been recruited. This suggests that the drug might be very active.”