FDA Approves Keytruda Plus Chemotherapy for Biliary Tract Cancer

The FDA has approved pembrolizumab (Keytruda; Merck) combined with gemcitabine and cisplatin for the treatment locally advanced unresectable or metastatic biliary tract cancer (BTC). This latest approval for pembrolizumab is the sixth indication for the anti-PD-1 therapy for gastrointestinal cancers.

“Cancers of the biliary tract can be highly aggressive tumors, underscoring the need for additional treatment options for the growing number of patients facing this challenging disease,” Robin Kate Kelley, MD, professor of clinical medicine in the division of hematology/oncology, University of California, San Francisco, said in a press release. “Today’s approval of pembrolizumab in combination with chemotherapy offers patients with locally advanced unresectable or metastatic biliary tract cancer a new immunotherapy regimen that has demonstrated the potential to help these patients live longer.”

The FDA action was based on findings from the phase 3 KEYNOTE-966 trial (NCT04003636). The trial’s primary efficacy outcome measure was overall survival (OS), with additional efficacy outcome measures of progression-free survival, objective response rate, and duration of response as assessed by blinded independent central review according to RECIST v1.1 criteria.

The trial showed that pembrolizumab plus chemotherapy lowered the risk of death by 17% (HR=0.83 [95% CI, 0.72-0.95]; one-sided p=0.0034) compared to chemotherapy alone at the pre-specified final analysis for OS. Further, median OS was 12.7 months (95% CI, 11.5-13.6) among patients administered pembrolizumab plus chemotherapy compared with 10.9 months (95% CI, 9.9-11.6) for patients administered chemotherapy alone.

Immune-mediated adverse events (AEs) reported during or after treatment with pembrolizumab include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. These immune-mediated AEs may not include all possible severe and fatal immune-mediated AEs, according to Merck.

Because of the severity of these AEs, pembrolizumab should be paused or permanently discontinued if they are reported, with corticosteroids administered if appropriate, according to Merck. Pembrolizumab can also lead to severe or life-threatening infusion-related reactions.

BTC is comprised of a group of rare and highly aggressive cancers that occur in the liver, gallbladder, and bile ducts. It is the second most common type of primary liver cancer after hepatocellular carcinoma and comprises approximately 15% of all liver cancers. Approximately 20,000 patients in the United States are diagnosed with BTC on an annual basis.

BTC most frequently occurs among patients between 50 and 70 years of age, with approximately 70% of patients diagnosed with the disease at an advanced stage. Patients with BTC often have a poor prognosis, with a 5-year relative survival rate of only 2%-3% for patients with advanced disease and 9%-11% for patients across all disease stages.

To date, more than 1600 trials are evaluating pembrolizumab across a range of cancer types and treatment settings. Pembrolizumab also has approved indications in melanoma; non-small cell lung cancer; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; gastric cancer; microsatellite instability-high or mismatch repair deficient cancer; microsatellite instability-high or mismatch repair deficient colorectal cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden-high cancer; cutaneous squamous cell carcinoma; and triple-negative breast cancer.

“Many patients with biliary tract cancer are diagnosed with locally advanced or metastatic disease, at which point they are not eligible for surgery and face poor survival outcomes with limited treatment options,” Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, said in a press release. “With this approval, Merck is proud to offer a new treatment option to certain patients with locally advanced unresectable or metastatic biliary tract cancer, and their healthcare providers, that has shown an overall survival benefit compared to chemotherapy alone.”

Reference

FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Gemcitabine and Cisplatin as Treatment for Patients With Locally Advanced Unresectable or Metastatic Biliary Tract Cancer. Merck. News release. November 1, 2023. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-gemcitabine-and-cisplatin-as-treatment-for-patients-with-locally-advanced-unresectable-or-metastatic-biliary-tract-cancer/