Molecular Profiling Should Now Be Routine Practice in Patients with CCA

September/October 2021, Vol 2, No 3
Milind M. Javle, MD
Hubert L. and Olive Stringer Professor
GI Medical Oncology
University of Texas MD Anderson
Cancer Center, Houston
Chair, NCI Task Force,
Hepatobiliary Cancers

Dear Colleagues,

This issue of CCA News features yet another exciting FDA approval for cholangiocarcinoma (CCA), ivosidenib, which was recently approved for CCA with IDH1 mutation. This is the third drug approved for CCA in the past 2 years, highlighting the critical role of molecular profiling in this cancer. Up to 20% of patients with intrahepatic CCA have IDH1 mutation, and the ClarIDHy phase 3 study demonstrated improvement in progression-free survival with ivosidenib versus placebo for chemorefractory disease. The FDA also approved the Oncomine Dx Target Test for IDH1 mutations.

At the CCA Summit during the 2021 American Society of Clinical Oncology meeting, Mitesh J. Borad, MD, from the Mayo Clinic in Phoenix reviewed some of the key topics presented. The FIGHT-202 updated results showed an overall response rate (ORR) of 37%, with an 8.1-month duration of response—remarkable figures for chemorefractory CCA with FGFR2 fusions. The FOENIX-CCA2 study revealed that the ORR with futibatinib was 41.7%, and the median duration of response was 9.7 months, along with a favorable impact on quality of life.

FGFR2 fusions occur in 10% to 16% of patients with intrahepatic CCA, according to a real-life study by Rachna T. Shroff, MD, from the University of Arizona Cancer Center, and colleagues, who reviewed 500 patients with CCA. These patients may have a favorable prognosis. Shalini Makawita, MD, from M.D. Anderson Cancer Center, explored the mutational profiles of patients with IDH1/IDH2-altered CCA. These subtypes have a unique genetic profile compared with wild-type IDH, and these tumors have a low prevalence of genomic biomarkers. These data are important when studying primary resistance, and for future approaches to combination therapies.

In a recent review article, Tanios S. Bekaii-Saab, MD, of the Mayo Clinic in Phoenix, and colleagues emphasized the importance of next-generation sequencing for improving personalized treatment for CCA; it is critical that an FDA-approved test be used. Molecular profiling is, however, not routinely performed in patients with CCA, according to this article.

Megan C. Roberts, PhD, from the University of North Carolina at Chapel Hill, reported that the 2 main reasons for lack of genomic testing are clinical utility and relevance. Clearly, there is a role for education of oncologists, with programs such as Mutations Matter from the Cholangiocarcinoma Foundation. Access to the novel therapies for CCA remains challenging, and, therefore, expanded access programs, as highlighted by Melinda Bachini of the Cholangiocarcinoma Foundation, are of significant value for patients with this disease.

Bruno C. Odisio, MD, FSIR, Interventional Radiologist at M.D. Anderson Cancer Center, reviews several interesting articles in this issue from 2 interventional oncology meetings, including a study from Matthew T. Quirk, MD, of the University of California at Los Angeles, that disputes the dogma regarding metastatic spread from transperitoneal biopsies for CCA, and another study from Germany, on the role of intra-arterial SIR-spheres therapy (or radioembolization) for CCA. Liver-directed therapies are underutilized, and further investigation is needed.

Flavio G. Rocha, MD, Director of Research, Digestive Disease Institute at the University of Washington in Seattle, has provided a succinct review of abstracts from the 2021 Americas Hepato-Pancreato-Biliary Association meeting. Natalia Paez-Arango, MD, and Hop S. Tran Cao, MD, of M.D. Anderson Cancer Center, reported their experience with neoadjuvant chemotherapy for intrahepatic CCA; this approach appears feasible and may prolong survival, although tissue assessment for pathologic response remains challenging.

Guergana Panayotova, MD, and Keri E. Lunsford, MD, PhD, from Rutgers, New Jersey Medical School, analyzed SEER data showing that liver transplantation, along with surgery, offered the best survival for intrahepatic CCA. These and other important developments are featured in this issue.

We look forward to your participation in the upcoming 3rd Annual CCA Summit, October 21-22, 2021, in New Orleans!


Milind Javle, MD

Milind M. Javle, MD
Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
The University of Texas
M.D. Anderson Cancer Center
Houston, TX
NCI Task Force: Hepatobiliary Cancers

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