Highlights
- •First randomized trial with targeted agent in refractory biliary cancer patients.
- •Trametinib was generally well tolerated in refractory biliary cancer patients.
- •There is unlikely benefit with trametinib in refractory biliary cancer patients.
Abstract
Background
The rationale for the evaluation of trametinib in advanced biliary cancer (BC) is
based on the presence of mitogen-activated protein kinase alterations and on earlier
promising results with MEK inhibitors in BC.
Methods
Patients with histologically proven BC who progressed on gemcitabine/platinum were
randomised to trametinib daily (arm 1) versus fluoropyrimidine therapy (infusional
5-fluorouracil or oral capecitabine, arm 2). The primary end-point was overall survival
(OS). Secondary end-points included progression free survival (PFS) and response rate.
A planned interim futility analysis of objective response was performed on the first
14 patients registered to the trametinib arm.
Results
The study was stopped early based on the lack of measurable response in the trametinib
arm. A total of 44 eligible patients were randomised (24 patients in arm 1 and 20
patients in arm 2). Median age was 62 years and the primary sites of tumour were cholangiocarcinoma
(68%) and gallbladder (32%). The overall response rate was 8% (95% CI 0%–19%) in arm
1 versus 10% (95% CI 0%–23%) in arm 2 (p > .99) Median OS was 4.3 months for arm 1
and 6.6 months for arm 2. The median PFS was 1.4 months for arm 1 and 3.3 months for
arm 2.
Conclusions
This is the first prospective randomised study of a targeted agent versus chemotherapy
for the second-line treatment of BC. In this unselected population, the interim analysis
result of unlikely benefit with trametinib resulted in early closure.
Keywords
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Article info
Publication history
Published online: March 29, 2020
Accepted:
January 22,
2020
Received in revised form:
January 16,
2020
Received:
April 29,
2019
Identification
Copyright
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