Pembrolizumab/Chemo Improves Survival Vs Chemo Alone in Biliary Tract Cancer

Pembrolizumab (Keytruda) plus chemotherapy compared with chemotherapy alone demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in the first-line treatment of patients with advanced or unresectable biliary tract cancer, according to a press release on findings from the final analysis of the phase 3 KEYNOTE-966 trial (NCT04003636).

The manufacturers of pembrolizumab "are very encouraged by these [overall survival] results" from the phase 3 KEYNOTE-966 study, which "show the potential benefit of [pembrolizumab] in addition to chemotherapy for [patients with] biliary cancer who are in urgent need of new treatment options."

In the trial, the pembrolizumab regimen also produced a safety profile that was consistent with those observed in previous studies. Investigators intend to share the results at a future medical meeting and submit them to regulatory authorities.

“We are very encouraged by these [OS] results that show the potential benefit of [pembrolizumab] in addition to chemotherapy for [patients with] biliary cancer who are in urgent need of new treatment options,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said in the press release.

Investigators of the randomized, double-blind phase 3 KEYNOTE-966 trial assessed pembrolizumab plus gemcitabine (Gemzar) and cisplatin (Platinol) compared with placebo and the same chemotherapy backbone as a first-line therapy for patients with advanced or unresectable biliary tract cancer.

In the experimental arm, patients received 200 mg of pembrolizumab intravenously once every 3 weeks on day 1 of each 3-week cycle for up to 35 cycles plus 1000 mg/m2 of intravenous gemcitabine once every 3 weeks on days 1 and 8 plus 25 mg/m2 of intravenous cisplatin once every 3 weeks on day 1 and day 8 for up to 8 cycles. Patients in the comparator arm received matched placebo along with the same chemotherapy backbone.

Secondary end points of the KEYNOTE-966 trial included progression-free survival, objective response rate, duration of response, adverse effects (AEs), and the number of patients who discontinued treatment due to AEs.

Patients 18 years and older with a histologically confirmed diagnosis of advanced or unresectable biliary tract cancer and measurable disease per RECIST v1.1 criteria were able to enroll on the study. Additional inclusion criteria included providing archival tumor tissue samples, having a life expectancy longer than 3 months, and adequate organ function.

Patients who received previous systemic therapy for advanced or unresectable biliary tract cancer or had ampullary cancer were unable to enroll on the study. Patients were also unsuitable for enrollment if they had small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, or mixed tumor histology; received prior therapy with an anti–PD-L1 agent; had a history of central nervous system metastases; or had an allogenic tissue or solid organ transplant.

Reference

Merck’s KEYTRUDA^® (pembrolizumab) plus chemotherapy significantly improved overall survival versus chemotherapy in first-line advanced or unresectable biliary tract cancer in KEYNOTE-966 trial. News release. Merck. January 25, 2023. Accessed January 26, 2023. bit.ly/3RaFegm