Health Canada approves Keytruda + chemotherapy as a first-line treatment for adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.- Merck Inc.,
Merck Inc., , known as MSD outside the United States and Canada, announced that Health Canada has granted approval of Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with fluoropyrimidine- and platinum-containing-chemotherapy, for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
This approval is based on the results from the Phase III KEYNOTE-859 trial , which demonstrated a statistically significant improvement in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) compared to placebo in combination with chemotherapy in the intention-to-treat (ITT) study population.
About KEYNOTE-859 : KEYNOTE-859 was a multicenter, randomized, double-blind, placebo-controlled Phase III trial (ClinicalTrials.gov NCT03675737) evaluating pembrolizumab in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma. The primary endpoint was overall survival (OS) with progression-free survival (PFS) and objective response rate (ORR) included as secondary endpoints as assessed by blinded independent central review (BICR) using RECIST v1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
The trial enrolled 1579 patients who had not previously received systemic therapy for metastatic disease and were randomized 1:1 to receive pembrolizumab (200 mg every three weeks) in combination with fluoropyrimidine- and platinum-containing chemotherapy (n=790), or placebo in combination with chemotherapy (n=789). All patients received investigator’s choice of chemotherapy (5-fluorouracil plus cisplatin [FP] or capecitabine plus oxaliplatin [CAPOX]). All study medications, except oral capecitabine, were administered as an intravenous infusion for every 3-week cycle. Platinum agents could be administered for 6 or more cycles following local guidelines. Treatment continued until RECIST v1.1-defined progression of disease as determined by BICR, unacceptable toxicity, or a maximum of 24 months.
A statistically significant improvement in OS, PFS and ORR was demonstrated in patients randomized to pembrolizumab in combination with chemotherapy compared with placebo in combination with chemotherapy at the pre-specified interim analysis of OS. In the study, there was a 22% reduction in the risk of death with pembrolizumab plus chemotherapy (HR=0.78 [95% CI, 0.70-0.87]; p<0.0001) versus chemotherapy alone. the median os for patients receiving pembrolizumab plus chemotherapy was 12.9 months (95% ci, 11.9-14.0) versus 11.5 months (95% ci, 10.6-12.1) for those receiving chemotherapy alone. a positive association was observed between pd-l1 cps score and the magnitude of the treatment benefit. the median duration of exposure to pembrolizumab was 6.2 months (range, 1 day to 33.7 months).>
The most common treatment-related adverse events ( greater than 20% incidence) for patients receiving pembrolizumab plus fluoropyrimidine- and platinum-containing chemotherapy were nausea, diarrhea, anemia, vomiting, platelet count decreased, neutrophil count decreased, palmar-plantar erythrodysesthesia syndrome, decreased appetite and fatigue.
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