Oral neratinib: Additional Phase II data

Puma reported additional data from the open-label Phase II I-SPY 2 trial in patients with newly diagnosed, stage >=2 breast cancer at a high risk for relapse at the American Association for Cancer Research in San Diego. In patients with HER2-positive/hormone receptor-negative breast cancer, oral neratinib plus paclitaxel followed by doxorubicin and cyclophosphamide led to an estimated pCR rate, the primary endpoint, of 55.6% vs. 32.6% for standard therapy consisting of paclitaxel plus Herceptin trastuzumab followed by doxorubicin and cyclophosphamide. The most frequently observed severe adverse event was diarrhea, with grade 3/4 diarrhea reported in 39% of patients in the neratinib arm vs. 4% in the control arm. The trial is designed to rapidly and inexpensively develop data to support small Phase III trials of new neoadjuvant therapies for locally advanced breast cancer or to help companies quickly kill ineffective candidates. I-SPY 2 involves an adaptive trial design based on Bayesian predictive probability that a regimen will be statistically superior to standard therapy in an equally randomized 300-patient confirmatory trial.

The Bayesian probability of superiority for the neratinib-containing regimen in patients with HER2-positive/hormone receptor-negative breast cancer compared to standard therapy is 94.9%, or p=0.051. Additionally, the Bayesian predictive probability of showing statistical superiority for the neratinib-containing regimen compared to standard therapy in a 300-patient Phase III trial is 79.1%. There were 115 patients assigned to neratinib in the trial, including 65 patients with HER2-positive breast cancer. In December, Puma said a neratinib-containing regimen "graduated" from I-SPY 2 based on having a high probability of success in patients with HER2-positive/hormone receptor-negative breast cancer in a Phase III trial (see BioCentury, Dec. 9, 2013). ...