Keytruda plus chemotherapy reduced risk of death by 27% versus chemotherapy as first-line treatment for locally advanced or metastatic esophageal cancer.- Merck Inc.

Merck announced first-time data from the pivotal Phase III KEYNOTE-590 trial evaluating Keytruda, Merck’s anti-PD-1 therapy, in combination with platinum-based chemotherapy (cisplatin plus 5-fluorouracil [5-FU]) for the first-line treatment of patients with locally advanced or metastatic esophageal and gastroesophageal junction (GEJ) cancer . In the study , Keytruda in combination with chemotherapy significantly improved overall survival (OS), reducing the risk of death by 27% [HR=0.73 [95% CI, 0.62-0.86]; p<0.0001], versus chemotherapy in all randomized patients. keytruda in combination with chemotherapy also significantly improved progression-free survival pfs reducing the risk of disease progression or death by 35 or more than a third hr="0.65" 95 ci 0.55-0.76 p><0.0001] in all randomized patients. with these results keytruda is the first anti-pd-1 therapy in combination with chemotherapy to show superior os pfs and objective response rates orr versus chemotherapy the current standard of care for these patients regardless of histology or pd-l1 expression status. these late-breaking data were presented during a presidential symposium at the european society for medical oncology esmo virtual congress 2020 abstract lba51. merck will be sharing these data with regulatory authorities worldwide. keytruda is currently approved in the u.s. china and japan as monotherapy for the second-line treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express pd-l1 combined positive score cps greater than 10. merck is continuing to study keytruda across multiple settings and stages of gastrointestinal cancer including gastric hepatobiliary esophageal pancreatic colorectal and anal cancers through its broad clinical program. keynote-590 is a phase iii randomized double-blind trial clinicaltrials.gov nct03189719 that enrolled 749 patients and is evaluating keytruda in combination with chemotherapy versus placebo plus chemotherapy cisplatin plus 5-fu for the first-line treatment of patients with locally advanced or metastatic esophageal carcinoma including esophageal squamous cell carcinoma escc and adenocarcinoma of the esophagus or siewert type 1 gej. the primary endpoints are os in patients with escc whose tumors expressed pd-l1 cps greater than 10 and os and pfs in patients with escc in all randomized patients whose tumors expressed pd-l1 cps greater than 10 and in all randomized patients. secondary endpoints include orr per response evaluation criteria in solid tumors recist v1.1 by investigator review in all patients duration of response dor and safety. os and pfs were tested using a hierarchical strategy such that testing was first performed in patients with escc whose tumors expressed pd-l1 cps greater than 10 with partial alpha passing from a successful test of the hypothesis then in all patients with escc then in all patients whose tumors expressed pd-l1 cps 10 and finally in all participants. at the first interim analysis after a median follow-up of 10.8 months keytruda in combination with chemotherapy demonstrated superior os versus chemotherapy in all randomized patients in the study hr="0.73" 95 ci 0.62-0.86 p><0.0001), in patients with escc whose tumors expressed pd-l1 cps greater than 10 hr="0.57" 95 ci 0.43-0.75 p><0.0001), in patients with escc hr="0.72" 95 ci 0.60-0.88 p="0.0006)," and in patients whose tumors expressed pd-l1 cps greater than 10 hr="0.62" 95 ci 0.49-0.78 p><0.0001). in all randomized patients in the study the median os was 12.4 months 95 ci 10.5-14.0 in the keytruda combination arm versus 9.8 months 95 ci 8.8-10.8 in the chemotherapy arm.in patients with escc whose tumors expressed pd-l1 cps greater than 10 the median os was 13.9 months 95 ci 11.1-17.7 in the keytruda combination arm versus 8.8 months 95 ci 7.8-10.5 in the chemotherapy arm.in patients with escc the median os was 12.6 months 95 ci 10.2-14.3 in the keytruda combination arm versus 9.8 months 95 ci 8.6-11.1 in the chemotherapy arm. in patients whose tumors expressed pd-l1 cps greater than 10 the median os was 13.5 months 95 ci 11.1-15.6 in the keytruda combination arm versus 9.4 months 95 ci 8.0-10.7 in the chemotherapy arm. keytruda in combination with chemotherapy demonstrated superior pfs versus chemotherapy in all randomized patients in the study hr="0.65" 95 ci 0.55-0.76 p><0.0001), in patients with escc hr="0.65" 95 ci 0.54-0.78 p><0.0001), and in patients whose tumors expressed pd-l1 cps greater than 10 hr="0.51" 95 ci 0.41-0.65 p><0.0001). in all randomized patients in the study the median pfs was 6.3 months 95 ci 6.2-6.9 in the keytruda combination arm versus 5.8 months 95 ci 5.0-6.0 in the chemotherapy arm. in patients with escc the median pfs was 6.3 months 95 ci 6.2-6.9 in the keytruda combination arm versus 5.8 months 95 ci 5.0-6.1 in the chemotherapy arm.in patients whose tumors expressed pd-l1 cps greater than 10 the median pfs was 7.5 months 95 ci 6.2-8.2 in the keytruda combination arm versus 5.5 months 95 ci 4.3-6.0 in the chemotherapy arm. keytruda in combination with chemotherapy demonstrated superior orr versus chemotherapy in all randomized patients in the study . the orr was 45.0 95 ci 39.9-50.2 in the keytruda combination arm versus 29.3 95 ci 24.7-34.1 in the chemotherapy arm p><0.0001). additionally the median dor was 8.3 months range 1.2 to 31.0 in the keytruda combination arm versus 6.0 months range 1.5 to 25.0 in the chemotherapy arm. treatment-related adverse events traes led to discontinuation in 19.5 of patients in the keytruda combination arm and 11.6 of patients in the chemotherapy arm. grade 3-5 traes occurred in 71.9 of patients in the keytruda combination arm and 67.6 of patients in the chemotherapy arm. there were nine treatment-related deaths in the keytruda combination arm and five treatment-related deaths in the chemotherapy arm. immune-mediated adverse events of any grade occurred in 25.7 of patients in the keytruda combination arm and 11.6 of patients in the chemotherapy arm.>