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.>