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 

 fusions or rearrangements, have treatment options, but there is a need of more active, durable therapies for the broader population, Kelley concludes.

Videos

R. Kate (Katie) Kelley, MD, discusses unmet needs and treatment challenges within the current standard-of-care for patients with cholangiocarcinoma.

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

R. Kate Kelley, MD, associate professor of clinical medicine, Department of Medicine, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discusses the rising incidence of hepatocellular carcinoma (HCC).

Obesity is a growing problem worldwide, and having obesity and risk factors for metabolic syndrome, including diabetes and dyslipidemia, can lead to HCC. Obesity can lead to a condition called nonalcoholic fatty liver disease, which is a spectrum of diseases, such as steatohepatitis.

Just like alcoholic hepatitis, hepatitis B, and hepatitis C, steatohepatitis can lead to fibrosis, cirrhosis, and the accumulation of mutations that can eventually lead to cancer. Associated conditions with nonalcoholic fatty liver disease are now the number 1 cause of HCC in the United States, says Kelley.

R. Kate Kelley, MD, associate professor of clinical medicine, Department of Medicine, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discusses the rising incidence of hepatocellular carcinoma.

Dr. Kelley Discusses the Rising Incidence of HCC

R. Kate Kelley, MD, associate professor, University of California, San Francisco, discusses the development of biomarkers for patients with hepatocellular carcinoma (HCC).

The potential of many therapies in development depends on identifying the patient groups most likely to benefit, explains Kelley. This will require a better understanding of the biology of HCC.

According to Kelley, the potential of new therapies will drive a wave of research to further define the relevant subgroups.

Dr. Kelley on the Development of Biomarkers for HCC

R. Kate Kelley, MD, associate professor, University of California, San Francisco, discusses biomarkers for immunotherapy in hepatocellular carcinoma (HCC).

In the advent of immunotherapy in HCC, there has been a renewed interest in determining biomarkers to find patients best suited for this treatment.

Following in the footsteps of other gastrointestinal malignancies, biomarkers like mutation burden may be a useful indicator, Kelley says. It is still too early to know, adds Kelley, as more data need to be collected to make a distinct analysis.

R. Kate Kelley, MD, associate professor, University of California, San Francisco, discusses biomarkers for immunotherapy in hepatocellular carcinoma.

R. Kate Kelley, MD

Articles

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

Dr. Kelley Discusses the Rising Incidence of HCC

Dr. Kelley on the Development of Biomarkers for HCC

Dr. Kelley Discusses Biomarkers for Immunotherapy in HCC