Biliary tract cancer has a poor prognosis, with a five-year overall survival (OS) rate of just 15%. However, results from the phase 2 ROAR trial demonstrated that almost every patient experienced some tumor reduction.
Trial participants had a median progression-free survival (PFS) exceeding nine months and a median OS of almost a year. The safety profile of dabrafenib/trametinib was consistent with previously reported clinical experience.
Researchers say that a better understanding of the tumor microenvironment, especially pertaining to signaling between normal tissue, stromal tissue, and tumor tissue, should provide insights regarding new therapeutic strategies.
Biliary cancer produces multiple mutations, including BRAF in about 5% of tumors overall. Previous studies of dabrafenib–trametinib, which inhibits BRAF and MEK, showed activity in other types of cancer associated with the BRAF V600E mutation, including melanoma, non–small-cell lung cancer, and anaplastic thyroid cancer.
There were no new or unexpected adverse events during treatment with dabrafenib–trametinib. The most common adverse events were pyrexia, rash, nausea, diarrhea, fatigue, and chills. In 37% of patients, adverse events led to dose reduction and in 54% to dose interruption. One patient experienced an adverse event that led to discontinuation.
Researchers noted that dabrafenib and trametinib should be considered a meaningful choice of treatment for patients with BRAF-mutant biliary tract cancer.
Source: MedPage Today, January 22, 2019