Dr Kelley on the Need for Additional Second-line Therapies in Cholangiocarcinoma

R. Kate (Katie) Kelley, MD, professor, Clinical Medicine, the Department of Medicine, Hematology and Oncology, the University of California, San Francisco (UCSF), affiliated faculty member, the Cancer Immunotherapy Program, UCSF, discusses unmet needs and treatment challenges within the current standard-of-care for patients with cholangiocarcinoma.

Treatment advancements with the addition of immune checkpoint inhibitors to standard-of-care chemotherapy consisting of gemcitabine and cisplatin have altered first-line treatment options for patients with biliary tract cancers and cholangiocarcinoma, Kelley begins, noting that data from the phase 3 TOPAZ-1 (NCT03875235) and KEYNOTE-966 (NCT04003636) trials were responsible for changing the standard of care in this space.

In the randomized, double-blind placebo controlled, international TOPAZ-1 trial, patients with advanced biliary tract cancer were treated with durvalumab (Imfinzi) or placebo in combination with gemcitabine and cisplatin in the first-line setting. The addition of durvalumab to chemotherapy resulted in significantly improved overall survival (OS) vs chemotherapy alone, and these findings supported the FDA approval of durvalumab in combination with gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancers in September 2022.

The randomized, double-blind KEYNOTE-966 trial evaluated pembrolizumab (Keytruda) plus gemcitabine and cisplatin compared with placebo plus gemcitabine and cisplatin. Findings demonstrated the addition of pembrolizumab led to an improvement in OS in patients with advanced or unresectable biliary tract cancer.

Although these trials represented improvement in the frontline setting, unmet needs still remain in second- and later-line settings, Kelley says, who notes that there has been little notable progress in later lines of therapy beyond some treatments for specific molecularly defined subgroups. Patients with targetable alterations, such as FGFR2 fusions or rearrangements, have treatment options, but there is a need of more active, durable therapies for the broader population, Kelley concludes.