Keytruda is Called a Blockbuster Drug and Deserves Its Reputation

As reported by the ICIJ, the FDA originally approved Keytruda (pembrolizumab) combined with cisplatin and gemcitabine on October 31, 2023, to treat locally advanced inoperable (unresectable) or cancer that has spread (metastatic) biliary tract cancer.

Interruption of pembrolizumab treatment due to AEs was necessary in 55% of patients, with the most common being decreased neutrophil count (18%), decreased platelet count (10%), anemia (6%), and decreased white blood cell count (4%).

The Agency’s approval was based on the results from the KEYNOTE-966 phase 3 trial (NCT04003636). Investigators observed a significant improvement in overall survival. The patients (N1069) were assigned randomly to the pembrolizumab arm (N533) or otherwise to chemotherapy alone (536).

The risk of death was reduced 17% in the combination arm when evaluating treatment with chemotherapy alone. When comparing the chemotherapy arm to the pembrolizumab arm the median overall survival was 10.9 months as opposed to 12.7 months respectively.

Pembrolizumab was administered at 200 mg on the first day of the cycle and 1000 mg/m2 of intravenous gemcitabine with 25 mg/m2 of intravenous cisplatin on the first and eighth day every three weeks.

Assessing Tumor Progression

Tumor progression was assessed by the investigators at six-week intervals for a maximum of fifty-four weeks and twelve weeks thereafter.

The patients continued with treatment until such time as disease progression or toxicity occurred. Pembroliziumab was administered for a maximum of thirty-five cycles. Cisplatin and gemcitabine were continued up to eight cycles. Patients who were receiving treatment benefits were allowed to receive the investigative combined treatment beyond the stated disease progression.

About the Primary Endpoint

Overall survival was established as the primary end point with secondary end points set as progression-free survival, objective response rate, and duration of response.

Overall survival final analysis report identified progression free survival as 6.5 months in the pembrolizumab cohort and 5.6 months in the chemotherapy cohort.

Investigators noted that statistical significance was not achieved. Median Response Rates for Pembrolizumab Cohort:

Overall response rate =29.0%
Complete response rate = 2.1%
Partial response rate = 27.0%
Duration of response = 8.3 months

Median Response Rates for the Chemotherapy Cohort:

Overall response rate =29.0
Complete response rate = 1.3%
Partial response rate =-27.0%
Duration of response = 6.8 months

Fifteen percent of patients in the trial discontinued treatment of Pembrolizumab due to adverse events such as pneumonitis (1.3%) of patients.

Additionally, pembrolizumab treatment was interrupted in 55% of patients with the most common occurrence reported to be a decrease in neutrophil counts (18%) as well as platelet count (10%), anemia (6%), and decreased white blood cell count (4l%)

AEs between both arms included pyrexia (26.0% vs. 20.0%), rash (21.0% vs. 13.0%), pruritus (15.0% vs. 10,0%) and hypothyroidism (9.0% vs. 2.6%), respectively. There were no clinically meaningful differences in grade 3/4 bAEs between arms.

“The approval of pembrolizumab in combination with chemotherapy has offered patients with locally advanced unresectable or metastatic biliary tract cancer an immunotherapy regimen that has demonstrated the potential to help these patients live longer,” lead study author Robin Kate Kelly, MD, professor of Clinical Medicine in the division of Hematology/Oncology at the University of California, San Francisco, said in the press release.

FDA approved Merck’s Keytruda (pembrolizumab) plus gemcitabine and cisplatin as treatment for patients with locally advanced unresectable or metastatic biliary tract cancer.

Contact Patient Worthy for specific updates, if you have questions, or if you would like to share your story with other patients or caregivers in the Patient Worthy Community

Rose Duesterwald August 17, 2026