Results from the phase 3 KEYNOTE-859 study show extended overall and progression-free survival in patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal adenocarcinoma treated with pembrolizumab and chemotherapy.
The combination of pembrolizumab (Keytruda) and chemotherapy demonstrated statistically significant and clinically meaningful improvements in overall survival as first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal (GEJ) adenocarcinoma.1
Results come from all patients randomized in the phase 3 KEYNOTE-859 (NCT03675737) clinical trial. The patient population also experienced statistically significant and clinically meaningful improvements in progression-free survival (PFS) and the overall response rate (ORR). Moreover, the safety profile of pembrolizumab in the trial was consistent with previously reported studies. No new safety signals were observed.
Full results from KEYNOTE-859 will be presented at an upcoming medical meeting and shared with regulatory authorities.
“Despite improvements in cancer care, advanced gastric cancer continues to have 1 of the lowest 5-year survival rates, and new interventions are urgently needed. The results from KEYNOTE-859 show the potential of [pembrolizumab] plus chemotherapy to improve survival beyond chemotherapy alone for patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression,” said Eliav Barr, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in a press release. “We are excited by these new results that demonstrate our commitment to exploring new treatment options for patients fighting gastrointestinal cancers with [pembrolizumab] and thank all investigators and patients who participated in this trial.”
The randomized, double-blind KEYNOTE-859 study includes approximately 1579 patients with HER2-negative, previously untreated, unresectable, or metastatic gastric or GEJ adenocarcinoma. Patients in the study are randomized to receive pembrolizumab 200 mg every 3 weeks for up to approximately 2 years in combination with fluoropyrimidine- and platinum-containing chemotherapy in the experimental arm or placebo in combination with chemotherapy in the control arm.2
OS is the primary end point of the study, and the secondary end points include PFS, ORR, duration of response, the percentage of patients with adverse events (AEs), and the percentage of patients who discontinue the study drugs due to AEs.
Patients aged 18 years or older were eligible to enroll in the study given they had histologically or cytologically confirmed disease, measurable disease per RECIST v1.1 criteria, archival or new tissue for biopsies and biomarker analysis, an ECOG performance status of 0 or 1, and adequate organ function.
If approved for HER2-negative locally advanced unresectable or metastatic gastric or GEC adenocarcinoma in the future, pembrolizumab will have more than 30 indications in solid tumors. In other gastric/GEJ cancer, pembrolizumab is already an approved first-line treatment in combination with trastuzumab (Herceptin), fluoropyrimidine- and platinum-containing chemotherapy, for patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma.
Pembrolizumab is also approved for the treatment of patients with locally advanced or metastatic esophageal or GEJ carcinoma that is not amenable to surgical resection or definitive chemoradiation, in combination with platinum- and fluoropyrimidine-based chemotherapy, or as a single agent after 1 or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
1. Merck announces phase 3 KEYNOTE-859 trial met primary endpoint of overall survival in patients with HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Merck. November 22, 2022. Accessed November 22, 2022. https://bit.ly/3OqwVvA
2. Pembrolizumab (MK-3475) plus chemotherapy versus placebo plus chemotherapy in participants gastric or gastroesophageal junction (GEJ) adenocarcinoma (MK-3475-859/KEYNOTE-859). ClinicalTrials.gov. Updated August 17, 2022. Accessed November 22, 2022. https://clinicaltrials.gov/ct2/show/NCT03675737?term=KEYNOTE-859&draw=2&rank=2