Dr Graff on Data From HER2CLIMB Exploratory Analysis in HER2+ Breast Cancer With Brain Metastases

Stephanie L. Graff, MD, director, breast oncology, Lifespan Cancer Institute, assistant professor of medicine, Warren Alpert Medical School, co-leader, Breast Cancer Translational Research Disease Group, Brown University’s Legorreta Cancer Center, discusses data from an exploratory analysis of patients with HER2-positive breast cancer and brain metastases enrolled to the phase 2 HER2CLIMB study (NCT02614794), and emphasizes the need for such research efforts to move the needle forward for this population.

Efforts to investigate the effect of current treatment approaches on brain metastases in patients with HER2-positive breast cancer have recently gained considerable traction and continue to expand, according to Graff. These patients are routinely excluded from clinical research due to concerns related to their higher risk status and poorer survival outcomes, as well as how these factors could affect data analysis, Graff explains. However, a significant proportion of patients with metastatic HER2-positive breast cancer will eventually develop brain metastases, making this an important population to investigate, Graff states.

The randomized, double-blind HER2CLIMB study investigated the use of tucatinib (Tukysa) plus capecitabine and trastuzumab (Herceptin) in patients with locally advanced or metastatic HER2-positive breast cancer who had been previously treated with docetaxel, trastuzumab, pertuzumab (Perjeta), or ado-trastuzumab emtansine (Kadcyla).

Of the 612 patients enrolled to the trial, 48% had brain metastases according to prior MRI screening, Graff says. Of these patients, 40% had stable treated brain metastases and 60% had active brain metastases. Patients with active brain metastases were further characterized according to whether they were previously treated or untreated.

In an updated exploratory analysis of this patient population, those with brain metastases experienced a statistically significant improvement in central nervous system (CNS) progression-free survival, as well as an approximate 9-month improvement in overall survival with the tucatinib-based regimen vs placebo. The tucatinib triplet reduced the risk of developing new brain lesions at the site of first progression or death by 45%, Graff notes. This indicates that both systemic disease and CNS disease are well controlled with the tucatinib-based approach, Graff concludes.

Editor’s Note: Dr. Graff reports serving in a consultory or advisory role for AstraZeneca, Daiichi Sankyo, Eli Lilly, Genentech, Novartis, Pfizer, Seattle Genetics.