Drug combination shows promise in rare GI cancers

A combination of dabrafenib and trametinib demonstrated promising efficacy in patients with rare gastrointestinal cancers linked to a mutation of the BRAF gene, according to research presented at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland.

Zev Wainberg, MD, of the department of medicine at UCLA, and colleagues explored the drug combination’s efficacy among patients with biliary tract cancer (BTC) and adenocarcinoma of the small intestine (ASI) who had previously received treatment with at least one line of systemic therapy. The median progression-free survival in both cancers is less than 5 months.

“These are patients with rare, aggressive cancers that have very poor prognoses and for which there are currently limited therapeutic options,” Wainberg said in a press release. “Their cancer has failed to respond to previous treatments — at least two prior chemotherapies had failed in 78% of them — so these are significant and promising results that provide proof that BRAF is a validated target in patients with biliary tract cancer."

In the phase 2, open-label study, patients with BRAF V600E mutations in nine rare tumor types, including BTC (n = 32) and ASI (n = 3), received continuous dabrafenib (Tafinlar, Novartis) plus trametinib (Mekinist, Novartis) until they had unacceptable toxicity, disease progression or died. The primary endpoint was investigator-assessed overall response rate (ORR). Researchers also explored duration of response, progression-free survival, overall survival and safety.

Wainberg and colleagues found that the ORR for patients in the BTC group was 41% (95% CI, 24%–59%) and 67% in the ASI group (95% CI, 9%-99%).

Of patients in the BTC group who responded, 54% had a duration of response of at least six months, while progression-free response was 7.2 months (95% CI, 4.6–10.1) and overall survival was 11.3 months (95% CI, 7.3–17.6).

“There is an urgent unmet need for these patients and we believe these exciting data represent a potential new treatment option for patients with this BRAF mutation,” Wainberg said in the release. – by Alex Young

Reference:

Wainberg Z, et al. Abstract 2LBA. Presented at: EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; November 13-16, 2018; Dublin, Ireland.

Disclosures: Wainberg reports consulting or advisory roles with Aduro Biotech, Array BioPharma, Bristol-Myers Squibb, Five Prime Therapeutics, Genentech, Lilly, Merck KGaA, Novartis, Pfizer, Plexxikon and Sirtex Medical.