The small-molecule HER2 inhibitor tucatinib showed “pivotal” improvements in progression-free survival (PFS) and overall survival (OS) for patients with metastatic HER2-positive (HER2+) breast cancer, according to results from phase II of the HER2CLIMB trial.
HER2CLIMB is an international, randomized at 2:1, double-blind, and placebo-controlled clinical trial. The tucatinib was administered in combination with trastuzumab and capecitabine and compared with trastuzumab and capecitabine alone.
Tucatinib resulted in a 46% reduction in the risk of disease progression or death (hazard ratio [HR]=0.54; 95% CI; 0.42, 0.71; P < 0.00001) compared the combination of trastuzumab (Herceptin) and capecitabine (Xeloda) alone, announced Seattle Genetics, Inc., on Monday.
“The addition of tucatinib to the commonly used doublet of trastuzumab and capecitabine represents a potential significant clinical advance for patients with metastatic HER2+ breast cancer, importantly, including those with brain metastases,” said Roger Dansey, MD, the chief medical officer of Seattle Genetics.
The first group of 480 patients had locally advanced or metastatic HER2+ and were treated previously with trastuzumab, pertuzumab (Perjeta), and T-DM1. Overall, a total of 612 patients were enrolled, starting in 2016.
Two secondary endpoints were met in the trial. The improvement in OS showed a 34% reduction in the risk of death (HR=0.66; 95% CI; 0.50, 0.88; P = 0.0048) with the addition of tucatinib, as compared with trastuzumab and capecitabine alone.
For patients with brain metastases, tucatinib group resulted in a 52% reduction in the risk of disease progression or death as compared with the non-tucatinib group (HR=0.48; 95% CI; 0.34, 0.69; P < 0.00001).
Grade 3 or greater adverse events in the experimental arm as compared to the control group included diarrhea (12.9% v. 8.6%), increased aspartate aminotransferase (AST) (4.5% vs 0.5%), alanine aminotransferase (ALT) (5.4% vs 0.5%) and bilirubin (0.7% vs 2.5%), according to the data.
Further results will be presented at the San Antonio Breast Cancer Symposium in December, Seattle Genetics added.
“Based on these findings, we plan to unblind the trial and offer tubactinib to patients on the control arm,” said Dansey, the company’s CMO. “We also plan to submit a New Drug Application to the FDA in the first quarter of 2020, with the goal of bringing a much-needed new medicine to patients.”
Seattle Genetics. A study of Tucatinib vs. Placebo in Combination with Capecitabine & Trastuzumab in Patient with Advanced HER2+ Breast Cancer (HER2CLIMB). Available from: https://clinicaltrials.gov/ct2/show/NCT02614794 NLM identifier: NCT02614794. Accessed October 20, 2019.