FDA Approves Keytruda Plus Chemo for Locally Advanced, Metastatic Biliary Tract Cancer

The Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) plus the chemotherapy drugs, gemcitabine and cisplatin, for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer, according to Merck, the manufacturer of Keytruda.

The approval was based on findings from the phase 3 KEYNOTE-966 clinical trial, which involved 1,069 patients and showed that the Keytruda-chemotherapy combination improved overall survival (time from treatment until death of any cause) by reducing the risk of death by 17% compared to chemotherapy alone. Of note, the median overall survival was 12.7 months in the Keytruda-containing group, compared to 10.9 months in the chemotherapy-only group.

According to a pre-specified final analysis of KEYNOTE-966, adding Keytruda to chemotherapy also showed a trend toward improved progression-free survival (time from treatment until disease worsening or death) over chemotherapy alone, with median progression-free survival times of 6.5 months and 5.6 months, respectively. However, the difference between the two groups’ progression-free survival was not statistically significant, meaning that researchers cannot be sure that one regimen is superior than the other regarding this outcome.

Twenty-nine percent of patients in the Keytruda group responded to therapy, with a complete response rate (percentage of patients whose disease disappears) of 2.1%, and a partial response (disease shrinks) rate of 27%. The response rate for the chemotherapy-only group was also 29%, with complete response and partial response rates of 1.3% and 27%, respectively.

“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,” Dr. Robin Kate Kelley, professor of clinical medicine in the division of hematology/oncology, University of California, San Francisco, said in a press release issued by Merck. “Today's approval of (Keytruda) 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.”

Keytruda works by helping the patient’s immune system find and fight the cancer. In doing so, patients may experience immune-related side effects, which can be severe or fatal and affect any organ. Common immune-related side effects include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin toxicities or solid organ transplant rejection. It is essential that patients bring up any side effects to their health care providers so that they can be addressed quickly and ensure the best outcome.

READ MORE:Immunotherapy Side Effects: ‘No Organ System Potentially Unaffected’

The side effect that led to the permanent discontinuation of Keytruda treatment was pneumonitis. The most common side effects or lab abnormalities that led to interruption of Keytruda therapy were decreased neutrophil count (18%), decreased platelet count (10%), anemia (6%), decreased white blood count (4%), pyrexia (3.8%), fatigue (3%), cholangitis (2.8%), increased alanine aminotransferase, which could indicate liver disease (2.6%), increased aspartate aminotransferase (AST) (2.5%) and biliary obstruction (2.3%).

Of note, there was no significant difference in grade 3 or 4 side effects between the Keytruda-containing and chemotherapy-only arms.

“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,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “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 health care providers, that has shown an overall survival benefit compared to chemotherapy alone.”

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