A message to those treating BTC: 'We encourage all oncologists to do this as early as possible'

Given biliary tract cancers' aggressive disease course and poor clinical outcomes, its not uncommon for a front-line option to fail. Gemcitabine and cisplatin-based chemotherapy can be chemo-resistant, which further confounds treatment.^[] What's the best course of treatment then?

Many oncologists turn to molecular profiling for actionable targets.

“Biliary tract cancer might be rare, but it's very target rich and kind of punches above its weight,” says Shubham Pant, MD, professor in department of gastrointestinal medical oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, in an interview with MDLinx.

Recommendation: Leverage the tech early on

Advanced molecular profiling technologies, including next-generation sequencing (NGS), are providing deeper insights into disease biology—now at a lower cost.

NGS has helped identify actionable mutations—such as IDH1, FGFR2, and HER2—that not only guide targeted therapies but also correlate with distinct clinical outcomes. As a result, precision medicine has become a routine part of BTC management.

“We encourage all oncologists to try to do molecular profiling as early as possible during the patient journey so that we know what options are available if the patients start progressing the front line," says Dr. Pant. "You're ready with your second-line option and you don't have to wait to get those results back."

Top targetable mutations to know

Top targets and associated therapies include:

• Ivosidenib for IDH1 tumors

• Futibatinib and pemigatinib for FGFR tumors

• Trastuzumab and zanidatamab for HER2 tumors

But benefits of molecular profiling extend past identifying IDH1, FGFR, and HER2 tumors, according to Dr. Pant.

“You might find needles in the haystack other than these three big ones,” he says. “Think about it like lung cancer; it’s a very target-rich disease.”

Limitations to consider

Both RET fusions and BRAF V600E are more uncommon molecular targets that can be identified by NGS. One limitation in the treatments of these targeted mutations, however, is that potential interventions are based on single-arm studies, as these mutations are rare.

A biliary tract tumor harboring more than one targetable mutation is also rare because the prevalence of any one target is between 5% and 10%, explains Dr. Pant.

“If I were to ever get [such a case], I would target one mutation and then target the other mutation," he says.