Biliary tract cancers (BTCs) are rare, aggressive malignancies that generally have a poor prognosis, and are usually treated with chemotherapy.
A new study shows that in a subgroup of these patients, individuals who have tumors with BRAF V600E mutations, treatment with a combination of targeted agents showed promising activity.
The combination of drugs used — the BRAF kinase inhibitor dabrafenib (Tafinlar, Novartis) and the MEK inhibitor trametinib (Mekinist, Novartis), is already approved for use in melanoma with BRAF V600 mutations.
Results of this drug combination in patients with BRAF-mutated biliary tract cancer, a cohort within the larger ROAR basket trial, were presented here at the Gastrointestinal Cancers Symposium (GICS) 2019.
There was an overall response rate (ORR) of 42%, and at data cutoff, 5 of 14 responses are ongoing, and seven patients had a response lasting 6 months or longer, said lead author Zev Wainberg, MD, codirector of the GI Oncology Program at the University of California, Los Angeles.
Median progression-free survival was 9.2 months and median overall survival was 11.7 months.
“Dabrafenib plus trametinib demonstrated clinical benefit in patients with BRAFmutant BTC and should be considered a meaningful therapeutic option for these patients,” Wainberg told the audience.
“The efficacy observed in this population of patients with advanced disease is comparable with that of first-line chemotherapy with gemcitabine and cisplatin,” he said.
Biliary Tract Cancer
Historically, the 5-year overall survival in biliary tract cancer patients is about 15%, but recurrence rates and prognosis may differ between extrahepatic and intrahepatic disease, explained Wainberg. The current standard of care includes resection and chemotherapy with gemcitabine and cisplatin. This regimen is associated with a progression free survival of 8 months and an overall survival of 11.7 months, which is similar to the results seen in this study with targeted agents, he commented.
Multiple mutations have been identified in association with biliary cancer, including BRAF in about 5% of overall tumors, and this “opens the possibility for targeted therapy in this population,” he said. “BRAF mutations may be enriched in intrahepatic BTC,” he added.
Potential Therapeutic Option
The combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has already demonstrated efficacy in other BRAF V600E cancers, including metastatic melanoma and melanoma in the adjuvant setting; non-small cell lung cancer; and anaplastic thyroid cancer.
–GDMeds, an India Pharmacy Service company
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