Complete Clinical Response of BRAF-Mutated Cholangiocarcinoma to Vemurafenib, Panitumumab, and Irinotecan

Excerpt

Cholangiocarcinoma is a rare tumor of the gastrointestinal tract characterized by poor prognosis and low sensitivity to cytotoxic therapy [1]. Some cholangiocarcinomas are known to contain BRAF mutations, which opens an opportunity for targeted treatment [2]. Use of single-agent inhibitors of mutated BRAF turned out to be successful in several tumor types, including melanomas, lung cancers, hematological malignancies, clear-cell sarcomas, etc. [3, 4]. However, BRAF mutation-driven cancers of gastrointestinal tract are largely insensitive to BRAF inhibition, possibly due to feedback activation of EGFR [3, 5, 6]. Combined targeting of BRAF and EGFR in colorectal malignancies provided promising results [3, 4, 7]. However, treatment of BRAF-mutated biliary tract cancers is more challenging, due to exceptionally rare occurrence of this tumor subtype and lack of standard efficient therapeutic options [1, 2]. Hyman et al. [3] treated with single-agent vemurafenib 8 patients with cholangiocarcinomas and observed only 1 partial response; low efficacy of vemurafenib monotherapy justifies the addition of other drugs to BRAF inhibitors while managing this tumor entity. …