Adding the PD-1 inhibitor pembrolizumab to gemcitabine and cisplatin led to a significant improvement in overall survival compared with gemcitabine and cisplatin alone as first-line therapy in patients with advanced or unresectable biliary tract cancer.
Adding the PD-1 inhibitor pembrolizumab (Keytruda) to gemcitabine and cisplatin led to a significant improvement in overall survival (OS) compared with gemcitabine and cisplatin alone as first-line therapy in patients with advanced or unresectable biliary tract cancer, according to topline findings from the phase 3 KEYNOTE-966 trial (NCT04003636).1
The safety profile of pembrolizumab was similar to that reported in prior trials. Full results will be presented at an upcoming medical meeting and will be submitted to regulatory agencies.
“Biliary tract cancer is typically diagnosed at an advanced stage, and these patients face a poor prognosis, with 5-year survival rates estimated to be approximately 5% to 15%,” Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer with Merck Research Laboratories, said in a press release. “We are very encouraged by these OS results that show the potential benefit of pembrolizumab in addition to chemotherapy for biliary cancer patients who are in urgent need of new treatment options.”
The announcement follows the release of the first positive read out of a phase 3 trial showing improved survival with the addition of immunotherapy to standard frontline chemotherapy in this population.2 The TOPAZ-1 trial (NCT03875235) demonstrated an improvement in median OS with the frontline combination of durvalumab (Imfinzi), gemcitabine, and cisplatin compared with gemcitabine and cisplatin alone (12.8 vs 11.5 months, respectively; HR, 0.80; 95% CI, 0.66-0.97; P = .021).
On September 2, 2022, the FDA approved the PD-L1 inhibitor durvalumab in combination with gemcitabine and cisplatin for the treatment of adults with locally advanced or metastatic biliary tract cancers.3
KEYNOTE-966 is a randomized, double-blind phase 3 trial evaluating pembrolizumab in combination with gemcitabine and cisplatin compared with placebo plus gemcitabine and cisplatin for the first-line treatment of advanced and/or unresectable biliary tract cancer. To be eligible for enrollment, adult patients had to have histologically confirmed metastatic or unresectable biliary tract cancer, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and no prior systemic therapy for advanced disease. Patients with past or ongoing hepatitis C or controlled hepatitis B virus infection are eligible per protocol-defined criteria.4
The trial enrolled 1069 patients, who were randomly assigned to 200 mg intravenous (IV) pembrolizumab every 3 weeks for up to approximately 2 years plus 1000 mg/m2 of IV gemcitabine and 25 mg/m2 of cisplatin on days 1 and 8 of every 3-week cycle. Patients in the control group were assigned to placebo plus gemcitabine and cisplatin on the same schedule.
Pembrolizumab will be continued for up to 35 cycles or until progression, unacceptable toxicity, or withdrawal. Gemcitabine will be continued until progression, unacceptable toxicity, or withdrawal. Cisplatin will be given for a maximum of 8 cycles.
The primary end point was OS, and the secondary end points included progression-free survival, objective response rate, duration of response, and safety.
Exploratory end points include disease control rate and health-related quality of life. Tumor imaging by CT or MRI will be performed every 6 weeks until week 54, and every 12 weeks thereafter. Adverse effects will be monitored throughout the study and graded according to NCI CTCAE v.5.0 criteria.