Hot Topics in Cholangiocarcinoma and Biliary Tract Cancer Discussed at Recent 2021 Meetings

Rachna T. Shroff, MD, MS, University of Arizona Cancer Center, Tucson, delivered a Keynote Review at the 3rd Annual Summit of studies presented in several 2021 national and international meetings, highlighting advances in treatments targeting FGFR2, IDH1, and HER2 mutations and other alterations that led to recently approved new therapies. She reminded attendees that in 2021, 2 new targeted therapies have been approved by the FDA for patients with cholangiocarcinoma (CCA).

Dr Shroff discussed the updated data presented for infigratinib, showing an objective response rate (ORR) of 34% in patients who received ≤1 lines of previous therapy and 13.8% in patients who received ≥2 lines of previous therapy. The median progression-free survival (PFS) was 7.3 months. Based on these data, the FDA approved infigratinib for second-line therapy in patients with CCA and an FGFR2 aberration.

The updated data from the FIGHT-202 study with pemigatinib demonstrated 37% ORR, with an updated median PFS of 7 months and overall survival (OS) of 17.5 months. Of the patients who responded to pemigatinib therapy, the median OS was 30.1 months. In a small study in Chinese patients, pemigatinib was found to be effective and well-tolerated in these patients.

In the pivotal phase 2 FOENIX-CCA2 study, among patients who received futibatinib, the ORR was 41.7%, and the median duration of response was 9.7 months.

In patients who received derazantinib, the ORR was 21%, the disease control rate was 76%, and the median PFS was 8 months.

“We also are trying to understand the natural history of patients with targeted therapy, and the importance of getting better and into the weeds of what these patients—patients with IDH, patients with FGFR, or patients with HER2 mutations—how these patients do on gemcitabine and cisplatin,” said Dr Shroff.

Gunagratinib is an irreversible FGFR inhibitor, with a potential to overcome acquired resistance to first-generation FGFR inhibitors.

In a study of ivosidenib in patients with CCA, among patients who received this drug, 70% were crossed over from the placebo arm, and most patients continued treatment for at least 1 year. The risk for disease progression was reduced by 63% with ivosidenib compared with placebo. The final OS analysis demonstrated numerically improved median OS—10.3 months versus 7.5 months. These data led to the FDA approval of ivosidenib as second-line therapy in patients with CCA and IDH1 mutation.

Recent data presented for zanidatamab demonstrated a 40% confirmed ORR in a refractory population of patients with HER2 overexpression. Chemotherapy combinations have also demonstrated improved ORR and survival outcomes.

“There is incredible momentum in biliary tract cancer drug development, and we are learning more and more about the biology of relevant targets, and how to manage resistance,” said Dr Shroff. “We continue to explore immunotherapy, and how we can make these cold tumors hot.”

According to Dr Shroff, the combination of gemcitabine and cisplatin remains “king,” but anticipated data from the TOPAZ-1, KEYNOTE-966, and the SWOG 1815 clinical trials may reveal more beneficial therapies than gemcitabine and cisplatin in patients with biliary tract cancers. She expects that 2022 will be a year to remember for patients with CCA.