Highlights
- •CISGEM-durvalumab is a new standard in advanced cholangiocarcinoma in first line.
- •Actionable alterations are present in up to 40–50% of patients, especially in iCCA.
- •Molecular profiling should be proposed to every ECOG 0–1 patients from the diagnosis.
- •Molecular profiling should integrate DNA and RNA next-generation sequencing techniques.
Abstract
Cholangiocarcinoma is a deadly cancer comprising very heterogenous subtypes with a
limited therapeutic arsenal in all comers. However, recent significant advances were
made with immunotherapy in the first-line treatment of advanced cholangiocarcinoma,
with the addition of durvalumab to cisplatin–gemcitabine chemotherapy showing a survival
benefit. In the second line setting, only FOLFOX (5FU/folinic acid-oxaliplatin) is
validated by a phase 3 trial, yet with a very modest benefit on survival; new options
using 5FU with nanoliposomal-irinotecan may emerge in the next few years. The advent
of molecular profiling in advanced cholangiocarcinoma in the last decade revealed
frequent targetable alterations such as IDH1 mutations, FGFR2 fusions or rearrangements,
HER2 amplification, BRAF V600E mutation and others. This strategy opened the way to
personalised medicine for patients which are still fit after first-line treatment
and the use of targeted inhibitors in first line constitutes a huge challenge with
many ongoing trials to improve patients’ care.
This review exposes the recent clinical trial findings in non-molecularly selected
advanced cholangiocarcinoma, offers a focus on how systematic molecular screening
should be structured to allow patients to access to personalised medicine, and details
which are the therapeutic options accessible in case of actionable alteration.
Keywords
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Article info
Publication history
Published online: December 02, 2022
Accepted:
November 5,
2022
Received in revised form:
October 31,
2022
Received:
August 24,
2022
Identification
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