Doctors Review the Current Biliary Tract Cancer Treatment Algorithm
Key Points
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The treatment algorithm for resectable biliary tract cancer for the majority of patients is surgery followed by adjuvant capecitabine.
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For unresectable or locally advanced patients, a multidisciplinary approach is critical to incorporate radiation therapy modalities.
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In metastatic biliary tract cancer, frontline treatment is typically cisplatin and gemcitabine plus durvalumab or pembrolizumab.
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Targeted agents are approved for metastatic biliary tract cancer in later treatment lines, so biomarker and mutation testing are crucial.
Treatment Algorithms for Biliary Tract Cancer
On the Oncology Brothers podcast, cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, spoke with Suneel Kamath, MD, a gastrointestinal medical oncologist at Cleveland Clinic, to discuss the treatment algorithm for resectable, unresectable, and metastatic biliary tract cancer.
Resectable Biliary Tract Cancer Treatment Algorithm
The predominant treatment algorithm for early, resectable biliary tract cancer is surgery followed by adjuvant capecitabine. Some studies have explored adding gemcitabine to adjuvant capecitabine. This combination may be appropriate for some patients, such as those already receiving additional adjuvant radiotherapy because of positive margins or similar features. These cases are relatively uncommon, however, and adjuvant capecitabine alone is appropriate for the majority of resectable patients, said Dr. Kamath.
For unresectable or locally advanced tumors, the treatment algorithm consists of chemotherapy, radiotherapy, or both. Localized modalities include stereotactic body radiation therapy, transarterial radioembolization, and transarterial chemoembolization. Some patients might also immediately start one of the systemic chemotherapy plus immunotherapy combinations used as frontline regimens in the metastatic or advanced setting. Overall, the doctors emphasized the importance of partnering with radiation colleagues to treat this population, as select patients who achieve a good response might be downstaged and become eligible for surgery or transplant.
Frontline Standard of Care for Metastatic Biliary Tract Cancer
The standard of care for metastatic biliary tract cancer in the frontline setting is cisplatin plus gemcitabine with either durvalumab or pembrolizumab. If renal dysfunction, hearing impairment, nausea, or vomiting are a concern with cisplatin, carboplatin or oxaliplatin can be substituted. The durvalumab triplet and pembrolizumab triplet were evaluated in the TOPAZ-1 and KEYNOTE-966 trials, and achieved median overall survival outcomes of 12.8 months and 12.7 months, respectively. When using either regimen, Dr. Kamath advocated for dropping the chemotherapy after 6 months and continuing patients on single-agent immunotherapy for improved tolerability. In addition, the chemotherapy–free interval may help patients tolerate fluorouracil (5-FU)–based regimens in later lines of therapy.
Metastatic Biliary Tract Cancer Treatment Options After Frontline Therapy
After frontline treatment, subsequent treatment options for metastatic biliary tract cancer include several targeted agents for patients with actionable mutations or biomarkers. For HER2–positive disease, trastuzumab deruxtecan (T-DXd) and single-agent zanidatamab are approved. Between the two, Dr. Kamath often favors zanidatamab for its more favorable toxicity profile. For patients with FGFR2 fusion, futibatinib, pemigatinib, and erdafitinib are approved. Dr. Kamath focuses on futibatinib and pemigatinib in these patients, but often favors futibatinib because of a slightly higher reported response rate.
Ivosidenib is approved for patients with an IDH1 mutation. Targeted therapy more often achieves disease control rather than a response, but remains a valuable option in the second-line setting, said Dr. Kamath. A small number of patients have also performed very well for multiple years on ivosidenib, he added.
In patients without actionable mutations or biomarkers, the treatment algorithm turns to 5-FU–based chemotherapy regimens like FOLFOX (leucovorin [folinic acid], 5-FU, and oxaliplatin) and FOLFIRI (leucovorin, 5-FU, and irinotecan). Most patients are likely to receive both regimens, but sequencing FOLFOXIRI (leucovorin, 5-FU, oxaliplatin, irinotecan) first may offer an advantage by breaking up concurrent platinum–based regimens. With either regimen, the doctors supported omitting the 5-FU bolus component. Ultimately, outcomes are not great in this population, and more effective therapies are needed, said Dr. Kamath.