ESMO TREATMENT ALGORITHM FOR BTC FOOTNOTES:

• Special considerations: (i) consider the need for preoperative drainage; (ii) avoid percutaneous biopsy in resectable d/pCCA; (iii) assess future liver remnant; (iv) neoadjuvant approach (selected cases); (v) completion surgery for incidental GBC stage ≥T1b.
• Salvage surgery or local therapies should be considered in responding patients with initially inoperable disease.
• FDA approved; not EMA approved.
• ESMO-MCBS v1.1 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluationforms).
• Reconsider surgery in the event of adequate response to treatment.
• Clinical trial recommended when available.
• Molecular profiling should be performed before/during first-line therapy. Gene panel should include FGFR2, IDH1, HER2/neu and BRAF to test for hotspot mutations but may also include genes such as NTRK and c-MET. The rapidly evolving landscape of drug targets and predictive biomarkers may necessitate larger panels in the future.
• Cisplatin–gemcitabine–durvalumab is recommended for first-line treatment [I, A]. Consider gemcitabine monotherapy in patients with a compromised PS or significant debility who are at risk of toxicity from platinum-containing ChT regimens. Was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmomcbs-evaluation-forms).
• ESCAT scores apply to genomic alterations only. These scores have been defined by the guideline authors and validated by the ESMO Translational Research and Precision Medicine Working Group.
• EMA and FDA approved.
• Anti-PD-1 therapy is recommended for patients with MSI-H/dMMR who have not been treated with first-line immunotherapy.
• EMA approved for MSI-H/dMMR BTC; FDA approved for all MSI-H/dMMR solid tumours.
• Not EMA approved; not FDA approved.

* in accordance with Evaluation form 2a

BTC=biliary tract cancer; dMMR=mismatch repair deficiency; EMA=European Medicines Agency; ESCAT=ESMO Scale for Clinical Actionability of Molecular Targets; ESMO=European Society for Medical Oncology; FDA=Food and Drug Administration; FGFR2=fibroblast growth factor receptor 2; FOLFOX=5-fluorouracil–leucovorin–oxaliplatin; GBC=gallbladder cancer; gem=gemcitabine; HER2=human epidermal growth factor receptor 2; iCCA=intrahepatic cholangiocarcinoma; IDH1=isocitrate dehydrogenase 1; MCBS=Magnitude of Clinical Benefit Scale; MDT=multidisciplinary team; MSI-H=microsatellite instabilityhigh; NCCN=National Comprehensive Cancer Network; NTRK=neurotrophic tyrosine receptor kinase; pCCA=perihilar cholangiocarcinoma; PD-1=programmed cell death protein 1; PS=performance status.