ESMO Clinical Practice Guideline interim update on the management of biliary tract cancer

Abstract

1. •

   This ESMO Clinical Practice Guideline update addresses new developments in the management of biliary tract cancer.

2. •

   Recommendations are given for first-line treatment with immune checkpoint inhibitors.

3. •

   Key recommendations are also provided for second-line treatment with targeted therapies.

4. •

   The update also covers the latest developments in molecular testing and intra-arterial therapies.

5. •

   A management algorithm for early-stage, locally advanced and advanced/metastatic disease is provided.

Keywords: biliary tract cancer (BTC); guideline; molecular diagnostics; treatment.

Figure 1

Management of BTC. Purple: algorithm title; orange: surgery; blue: systemic anticancer therapy or their combination; turquoise, non-systemic anticancer therapies or combination of treatment modalities; white: other aspects of management and non-treatment aspects; dashed lines: optional therapy. 5-FU, 5-fluorouracil; BTC, biliary tract cancer; CCA, cholangiocarcinoma; ChT, chemotherapy; dMMR, mismatch repair deficiency; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; FDA, Food and Drug Administration; FOLFOX, 5-fluorouracil–leucovorin–oxaliplatin; HER2, human epidermal growth factor receptor 2; iCCA, intrahepatic cholangiocarcinoma; MCBS, ESMO-Magnitude of Clinical Benefit Scale; MDT, multidisciplinary team; MSI-H, microsatellite instability-high; PARP, poly (ADP-ribose) polymerase; PD-1, programmed cell death protein 1; RFA, radiofrequency ablation; SBRT, stereotactic body radiotherapy. ^aClinical trial recommended when available. ^bMolecular profiling should be carried out before or during first-line therapy. Gene panel should include IDH1, FGFR2, BRAF, HER2,NTRK,RET, BRCA1/2 and PALB2 to test for hotspot mutations, but may also include genes such as c-MET. The rapidly evolving landscape of drug targets and predictive biomarkers may necessitate larger panels in the future. ^cSpecial considerations: (i) consider need for preoperative drainage; (ii) avoid percutaneous biopsy in resectable distal or perihilar CCA; (iii) assess future liver remnant; (iv) neoadjuvant approach (selected cases); (v) completion surgery for incidental gallbladder carcinoma stage ≥T1b. ^dSalvage surgery or local therapies should be considered in responding patients with initially inoperable disease. ^eConsider gemcitabine monotherapy in patients with compromised performance status or significant debility who are at risk of toxicity from platinum-containing ChT regimens. ^fReconsider surgery in the event of adequate response to treatment. ^gRegimen without a specific licensed indication in BTC. ^hESMO-MCBS v1.1 was used to calculate scores for therapies/indications approved by the EMA or FDA. The scores have been calculated and validated by the ESMO-MCBS Working Group and reviewed by the authors (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms). ⁱESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the authors and validated by the ESMO Translational Research and Precision Medicine Working Group.^jFDA approved, not EMA approved. ^kAnti-PD-1 therapy is recommended for patients with MSI-H or dMMR who have not been treated with first-line immunotherapy. ^lEMA approved for MSI-H or dMMR BTC; FDA approved for all MSI-H or dMMR solid tumours. ^mNot EMA or FDA approved.