Rocky Ride for Iniparib Not Yet Over

Iniparib, a PARP inhibitor being investigated for the treatment of metastatic triple-negative breast cancer (mTNBC), has gone from “hero to zero” since generating much excitement last year, says noted breast cancer researcher Chris Twelves, MD.

However, in a recent interview with OncLive, Twelves, a professor of clinical pharmacology and oncology at the Leeds Institute of Molecular Medicine in the United Kingdom, said that iniparib remains an intriguing therapeutic possibility despite failing to meet its phase III primary endpoints.

“We were probably a little carried away as a community by the phase II data and shouldn’t overreact until we’ve actually seen the phase III data,” he said.

The phase II trial results that raised hopes indicated that 56% of mTNBC patients who received iniparib demonstrated a clinical benefit as opposed to 34% of patients in the chemotherapy-only arm, with clinical benefit defined as a complete response, a partial response, or stable disease of at least 6 months. In addition, median overall survival in the iniparib group was 12.3 months, versus 7.7 months in the chemotherapy arm, representing a 43% improvement in the survival rate.

In January, however, sanofi-aventis announced that BSI-201, as iniparib also is known, did not meet the prespecified criteria for significance for its primary endpoints of overall survival and progression-free survival in a phase III trial. The study involved 519 women with mTNBC who were randomized to receive a standard chemotherapy regimen of gemcitabine and carboplatin with or without iniparib.

At the same time, sanofi-aventis said, patients treated in the second- and third-line setting demonstrated an improvement in overall survival and progression-free survival.

"While the phase III trial did not meet its primary endpoint, we believe that the demonstrated improvement in overall survival and progression-free survival in patients in the second- and third-line settings are important findings,” Charles Hugh-Jones, MD, vice president, US Medical Affairs Oncology for sanofi-aventis, said in a statement this week.

“The company is conducting an in-depth analysis to gain further insight into these results," he said.