The approval marks the sixth indication for pembrolizumab in gastrointestinal cancers.
The FDA has approved pembrolizumab (Keytruda; Merck) with gemcitabine and cisplatin to treat individuals with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Pembrolizumab is an anti-programed death receptor-1 (PD-1) therapy that is intended to increase the immune system's ability to detect and fight tumor cells. It is also a humanized monoclonal antibody that “blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2,” leading to the activation of T lymphocytes that could affect tumor and healthy cells.
“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,” said Robin Kate Kelley, PhD, professor of clinical medicine in the division of hematology/oncology at the University of California, San Francisco, 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.”
BTC is a group of aggressive cancers that are found in the liver, gallbladder, and bile ducts. The group of cancers are rare, although researchers noted that BTC IS the second most common type of primary liver cancer. The cancer impacts around 20,000 individuals each year, most of whom are 50 to 70 years old. The researchers noted that within the 20,000 individuals diagnosed, 70% are in an advanced stage of BTC, with a 2% to 3% 5-year survival rate.
The approval was based on results from the phase 3 KEYNOTE-966 trial, (NCT04003636) which was a multicenter, double-blind, randomized, placebo-controlled study. The researchers assessed pembrolizumab in combination with gemcitabine and cisplatin for the treatment of BTC for individuals that did not receive systemic therapy in the past, compared to chemotherapy unaided.
The trial included 1069 patients randomly assigned to 200 mg of pembrolizumab, 1000 mg of gemcitabine, and 25 mg of gemcitabine or a placebo with the same dosages of gemcitabine and cisplatin. The individuals received treatment on days 1 and 8 every 3 weeks and continued until reported unacceptable toxicity or disease progression. The usage of pembrolizumab continued for 35 cycles, amounting to 24 months.
The primary endpoint of the study was overall survival (OS). The results reduced the risk of death by 17% (HR=0.83 [95% CI, 0.72-0.95]) compared to the use of chemotherapy alone, according to the findings.
Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Patients undergoing treatment should be monitored closely for symptoms of underlying adverse reactions.
“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,” Kelley said. “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.”
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. Accessed 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/.