BTC quick hits: A clinical guide on HER2 amplification, 5 actionable biomarkers, and when to order NGS
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If we never look, we’ll never find it—and even rare alterations can have a profound impact on a patient’s treatment options.
—Douglas Rubinson, MD, PhD, Assistant Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School
Biliary tract cancers (BTCs) have historically lagged behind lung and other tumor types in realizing the full potential of precision oncology—but that gap is closing.
A growing body of data shows that a meaningful proportion of BTCs harbor actionable alterations, making early and repeated molecular testing increasingly central to care.
In a recent conversation with MDLinx, Douglas Rubinson, MD, PhD, Assistant Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School, outlined a practical approach to sequencing, highlighted high-yield biomarkers, and emphasized how even rare findings can open the door to effective targeted therapies.
Here are the key clinical takeaways.
When to biopsy and sequence
Initial comprehensive profiling is integral at the start of treatment, as rare alterations are uncommon individually but collectively meaningful. “I do it at diagnosis, and then I do it again after progression on targeted therapy,” Dr. Rubinson says.
To save time, rebiopsy can be done using liquid biopsy instead of solid biopsy.
5 actionable biomarkers
IDH1 mutations is targetable with ivosidenib.
FGFR2 fusions/translocations is targetable with pemigatinib futibatinib.
HER2 overexpression is targetable with zanidatamab (Ziihera).
BRAF mutations are targetable with BRAF + MEK inhibitor combinations.
Microsatellite instability-high (MSI-H) is found in approximately 1%–20% of cholangiocarcinomas and strongly responds to immunotherapy.
HER2 amplifications
HER2 amplifications and overexpression are frequently observed with gallbladder cancer.
Zanidatamab is a humanized bispecific antibody targeting juxtamembrane extracellular domain (ECD4) and the dimerization domain (ECD2) of HER2.
In clinical trials, zanidatamab has proven effective for patients with treatment-refractory HER2-positive biliary tract cancer.
The bottom line? According to Dr. Rubinson, “If we never look, we’ll never find it—and even rare alterations can have a profound impact on a patient’s treatment options.”