ASCO Highlights

Final results from the phase 3 clinical trial ClarIDHy showed that ivosidenib (Tibsovo), a first-in-class oral inhibitor of isocitrate dehydrogenase 1 (IDH1) mutation, prolonged the median overall survival (OS) in patients with previously treated advanced cholangiocarcinoma (CCA) and IDH1 mutation. Although this improvement did not reach statistical significance, after adjusting for crossovers from the placebo to the ivosidenib group, the difference in median OS was statistically significant.

Genomic alterations that are characteristic of intrahepatic cholangiocarcinoma (CCA) are well known. A study led by Jeffrey S. Ross, MD, Medical Director, Foundation Medicine, Cambridge, MA, examined whether genomic alterations from a primary tumor would differ from metastatic tumor tissue and liquid biopsy in patients with intrahepatic CCA. The study results were presented at the 2020 ASCO annual meeting.

Treatment with 6 months of adjuvant capecitabine chemotherapy is currently the standard of care in patients with resected extrahepatic cholangiocarcinoma (CCA). However, the benefit of treatment with adjuvant radiation therapy is not well-defined.

Mutations in IDH1 are detected in approximately 13% of patients with intrahepatic cholangiocarcinoma (CCA). ClarIDHy was a global, phase 3, double-blind clinical trial in previously treated patients with advanced intrahepatic CCA with IDH1 mutation.

In patients with locally advanced or metastatic biliary tract cancer, treatment with second-line chemotherapy is challenging after disease progression from first-line gemcitabine plus cisplatin, although treatment with modified FOLFOX (mFOLFOX) has been proven to be superior to active symptom control in the ABC-06 trial. Irinotecan (Camptosar) is an active drug used in the treatment of various gastrointestinal cancers.

Varlitinib is a reversible small-molecule, pan human epidermal growth factor receptor (HER) inhibitor with low nanomolar potency against HER1 (EGFR), HER2, and HER4.

Futibatinib is a highly selective irreversible fibroblast growth factor receptor (FGFR)1-4 inhibitor, administered as a continuous once-daily oral regimen. The FOENIX-CCA2 phase 2 clinical trial was initiated after the results from a phase 1 dose-escalation/expansion study showed the tolerability and preliminary efficacy of futibatinib in patients with intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions.

Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are emerging as promising therapeutic targets in patients with cholangiocarcinoma (CCA). A retrospective chart review, led by Lipika Goyal, MD, MPhil, Medical Oncologist, Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital, Boston, was performed in patients with CCA who had an FGFR alteration found by tumor molecular profiling as part of routine care.¹ Dr Goyal presented this study at the 2020 ASCO annual meeting.