Frontline pembrolizumab plus chemotherapy improves overall survival (OS), when compared with chemotherapy alone, in patients with advanced biliary tract cancer, according to results from the KEYNOTE-966 trial.
“KEYNOTE-966 … is the largest randomized phase 3 trial in advanced biliary tract cancers to date and one of very few positive phase 3 trials in this very difficult-to-treat family of cancers,” said Robin Kate Kelley, MD, of the University of California, San Francisco.
Dr Kelley presented results from KEYNOTE-966 at the AACR Annual Meeting 2023. The results were simultaneously published in The Lancet.
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The trial (ClinicalTrials.gov Identifier: NCT04003636) included 1069 patients with previously untreated, metastatic or unresectable biliary tract cancer. They were randomly assigned to receive pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or placebo. Both arms received gemcitabine (1000 mg/m2 on days 1 and 8 every 3 weeks with no maximum number of cycles) and cisplatin (25 mg/m2 on days 1 and 8 every 3 weeks for up to 8 cycles).
There were 533 patients in the pembrolizumab arm and 536 in the placebo arm. The median age at baseline was 64 years and 63 years, respectively. Most patients had metastatic disease (89% and 88%, respectively), and more than half had intrahepatic disease (60% and 58%, respectively).
The median follow-up was 25.6 months. The median OS was 12.7 months in the pembrolizumab arm and 10.9 months in the placebo arm (hazard ratio [HR], 0.83; 95% CI, 0.72-0.95; P =.0034). The 24-month OS rate was 25% and 18%, respectively.
There was no significant difference in progression-free survival (PFS) between the arms, but there was a trend toward improved PFS with pembrolizumab. The median PFS was 6.5 months in the pembrolizumab arm and 5.6 months in the placebo arm (HR, 0.87; 95% CI, 0.76-0.99). The 24-month PFS rate was 9% and 5%, respectively.
Overall response rates were similar between the arms — 29% in the pembrolizumab arm and 28% in the placebo arm. The median duration of response was 8.3 months and 6.8 months, respectively.
Grade 3-4 treatment-related adverse events (AEs) were reported in 70% of patients in the pembrolizumab arm and 69% of those in the placebo arm. Fatal treatment-related AEs occurred in 2% and 1% of patients, respectively.
The most common AEs of any grade and any cause (in the pembrolizumab and placebo arms, respectively) were decreased neutrophil counts (62% and 61%) and anemia (61% and 59%). Immune-mediated AEs occurred in 22% of patients in the pembrolizumab arm and 13% of those in the placebo arm.
“These data support pembrolizumab plus gemcitabine and cisplatin as a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer,” Dr Kelley said.
Disclosures: This research was supported by Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.
References
1. Kelley RK, Yoo C, Finn RS, et al. Pembrolizumab (pembro) in combination with gemcitabine and cisplatin (gem/cis) for advanced biliary tract cancer (BTC): Phase 3 KEYNOTE-966 study. AACR 2023. April 14-19, 2023. Abstract CT008.
2. Kelley RK, Ueno M, Yoo C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published online April 16, 2023. https://doi.org/10.1016/S0140-6736(23)00727-4
