The Lynx Group
Cholangiocarcinoma News

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

December 2021, Vol 2, No 4

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.

Related Items

A Global Perspective on CCA
By Virote Sriuranpong, MD, PhD
Dr Virote Sriuranpong provides a perspective on key issues facing Thailand and other Asian countries in the prevention, screening, and early diagnosis of CCA.
Molecular Targets in iCCA Surgical Candidates
By Keri Lunsford, MD, PhD, FACS; Alice Wei, MD, MSc, FRCSC, FACS
Drs Keri Lunsford and Alice Wei provide their perspectives on how the molecular profile of iCCA patients can help direct surgery and locoregional therapy.
Periadjuvant Therapy in iCCA
By Cristina Ferrone, MD; Shishir Kumar Maithel, MD, FACS
Dr Cristina Ferrone discusses the use of adjuvant therapy, and Dr Shishir Kumar Maithel speaks to the role of neoadjuvant therapy in patients with iCCA.
New Frontiers in Surgery for CCA
By Skye Mayo, MD, MPH, FACS; Alice Wei, MD, MSc, FRCSC, FACS
Drs Alice Wei and Skye Mayo discuss options for induction therapy prior to surgery in iCCA.
Transplantation in iCCA
By Keri Lunsford, MD, PhD, FACS; Maria B. Majella Doyle, MD, MBA, FRCSI, FACS
Drs Keri Lunsford and Maria Majella Doyle explore clinical data on neoadjuvant treatment before transplantation in patients with iCCA.
New Pathways and Molecular Targets in Cholangiocarcinoma
By Erin Burns, PhD
December 2021, Vol 2, No 4
Potential therapeutic targets for cholangiocarcinoma (CCA) include oncogenic pathways and other options, such as epigenetics, posttranslational modifications, and metabolism, according to presentations delivered during Session I, “Advances in Translational/Molecular Targets in CCA: New Molecular Targets/Pathways in CCA,” at the 3rd Annual CCA Summit.
Molecular Epidemiology of Cholangiocarcinoma: Identifying New Inherited Variants
By Erin Burns, PhD
December 2021, Vol 2, No 4
Cholangiocarcinoma (CCA) involves genetic heterogeneity, highlighting the need to identify new inherited variants, as discussed at the 3rd Annual CCA Summit in Session II, “Molecular Epidemiology of CCA.”
The Future of Chemotherapy in Cholangiocarcinoma
By Erin Burns, PhD
December 2021, Vol 2, No 4
Personalization of therapy and novel regimens are needed to improve options for patients with cholangiocarcinoma (CCA).
Understanding Predictive Biomarkers and Resistance to Immunotherapy in Biliary Tract Cancers
By Erin Burns, PhD
December 2021, Vol 2, No 4
Improved understanding of predictive biomarkers is needed in immuno-oncology, and various immunotherapy combinations using different mechanisms of action are being investigated in cholangiocarcinoma (CCA) and other biliary tract cancers, according to presentations delivered at Session IV, “What’s New in Immuno-­oncology in BTC? Monotherapy and Combo Therapies,” at the 3rd Annual CCA Summit.
Biomarker Testing and Imaging in Cholangiocarcinoma
By Erin Burns, PhD
December 2021, Vol 2, No 4
New biomarker technologies may be combined with cholangiocarcinoma (CCA) characteristics to predict patient response to treatment, according to presenters at Session V, “Biomarker Testing in CCA: New Technologies/­Imaging as a Biomarker,” during the 3rd Annual CCA Summit.

Subscribe to CCA News

Stay up to date with personalized medicine by subscribing to receive the free CCA News print publication or weekly e‑Newsletter.

I'd like to receive: