Novel investigational therapies for treating biliary tract carcinoma

ABSTRACT

Introduction: Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising from bile ducts and/or peribiliary glands. Even though it is considered as a rare neoplasm, its incidence is raising, particularly in developed countries. Prognosis is generally poor with few patients who present the inclusion criteria for surgery (the mainstay treatment for this tumour). Several genetic alterations potentially driving tumour progression have been described, representing a possible target for new compounds.

Areas covered: A clinical trial search in Clinicaltrials.gov encompassing a literature search in PubMed and ASCO/ESMO Websites was undertaken in March 2016.

Expert opinion: Notwithstanding a large number of drug tested, results are still disappointing. The main reasons could be the low number of patients enrolled in trials, and the lack of a patient selection based on the biological profile of the tumours. Potential active drugs could have been discharged simply because beneficial in a particular subgroup of patients and not in un unselected population. The future direction of the research should consider biomarker evaluation in order to describe the genetic alteration/s that drive tumour progression and aggressiveness and the mechanisms of drug resistance. Finally, it will be of great interest to consider the results of immunotherapy whenever available.

KEYWORDS:

• Cholangiocarcinoma review
• target therapy
• next generation sequencing
• prognostic biomarker

Article highlights

• Cholangiocarcinoma is a rare cancer and its incidence is raising particularly in developed countries. Many genetic alterations have been described, giving rationale for the development of new treatment strategies

• Anti-EGFR therapies have been extensively studied in cholangiocarcinoma patients. Notwithstanding encouraging preliminary results, comparison trials did not demonstrate superiority of cetuximab or panitumumab plus chemotherapy versus chemotherapy alone. A new pan-HER oral inhibitor is being tested

• Several specific inhibitors directed to mTor, ABL, PI3K/AKT, Farnesyltransferase, proteasome, and VEGF failed to demonstrate significant clinical activity in unspecific patient population.

• Results from trial selecting patients with specific genetic alterations (FGFGR, IDH, ALK, ROS1, NTRK) or from trial that explore the role of drugs with new mechanisms of action (oxygen modulators, pan-IDH1 mutant inhibitor, PARP 1/2 inhibitor) will help researchers to shed light on the mechanisms underlying tumour progression

• The characterization of the genetic profile of each single tumour will pave the way for personalized and hopefully efficacious therapies.

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Declaration of interest

M. Tampellini has received grants from Eli Lilly, Bayer Plc and Sanofi. G. V. Scagliotti has received grants from Eli Lilly and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.