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PMID
Authors K. Kato J-M. Sun M.A. Shah P.C. Enzinger A. Adenis T. Doi T. Kojima J-P. Metges Z. Li S-B. Kim B.C. Chul Cho W. Mansoor S-H. Li P. Sunpaweravong M.A. Maqueda E. Goekkurt Q. Liu S. Shah P. Bhagia L. Shen
Title LBA8_PR Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: The phase 3 KEYNOTE-590 study
Journal Vol Issue Date Pages Journal Short Title
Ann Oncol. 31 no. 4_suppl
URL https://www.annalsofoncology.org/article/S0923-7534(20)42380-4/fulltext
Abstract Text Background KEYNOTE-590 (NCT03189719) is a randomized, international, double-blind study of 1L pembrolizumab (pembro) + chemotherapy (chemo) vs chemo alone in patients (pts) with locally advanced/unresectable or metastatic adenocarcinoma or esophageal squamous cell carcinoma (ESCC) or Siewert type 1 esophagogastric junction adenocarcinoma (EGJ). Methods Eligible pts were randomized 1:1 to pembro 200 mg or placebo Q3W for up to 2 yr + chemo (cisplatin 80 mg/m2 Q3W [d1; 6 doses] + 5-FU 800 mg/m2 on d1-5 Q3W). Randomization was stratified by Asia vs Rest of World, adenocarcinoma vs ESCC, and ECOG PS 0 vs 1. Treatment continued until progression, unacceptable toxicity, or withdrawal, or 2 yr. No crossover was permitted. Primary end points were OS in pts with ESCC PD-L1 combined positive score (CPS) ≥10 tumors, and OS and PFS (RECIST v1.1 ; by investigator) in ESCC, PD-L1 CPS ≥10, and all pts. The secondary end point was ORR (RECIST v1.1; by investigator) in all pts. Data cutoff for interim OS/final PFS analysis was July 2, 2020. Results At data cutoff, 749 pts (83% male, 73% ESCC) were randomized (373 pembro + chemo; 376 chemo). Median follow-up was 10.8 mo. Pembro + chemo vs chemo was superior for OS in pts with ESCC CPS ≥10 (median 13.9 vs 8.8 mo; HR 0.57; 95% CI, 0.43-0.75; P < 0.0001), ESCC (median 12.6 vs 9.8 mo; HR 0.72; 95% CI, 0.60-0.88; P = 0.0006), CPS ≥10 (median 13.5 vs 9.4 mo; HR 0.62; 95% CI, 0.49-0.78; P < 0.0001), and all pts (median 12.4 vs 9.8 mo; HR, 0.73, 95% CI, 0.62-0.86; P < 0.0001). PFS was superior with pembro + chemo vs chemo in ESCC (median 6.3 vs 5.8 mo; HR 0.65; 95% CI, 0.54-0.78; P < 0.0001), CPS ≥10 (median 7.5 vs 5.5 mo; HR 0.51; 95% CI, 0.41-0.65; P < 0.0001), and all pts (median 6.3 vs 5.8 mo; HR 0.65; 95% CI, 0.55-0.76; P < 0.0001). Confirmed ORR was 45.0% vs 29.3% (P < 0.0001) in all pts, with median DOR of 8.3 vs 6.0 mo. Grade 3-5 drug-related AE rates were 72% vs 68%. Discontinuation rates from drug-related AEs were 19% vs 12%. Conclusions Pembro + chemo provided superior OS, PFS, and ORR vs chemo, with a manageable safety profile in pts with untreated, advanced esophageal and EGJ cancer. These data demonstrate that 1L pembro + chemo is a new standard of care in this pt population. Clinical trial identification NCT03189719.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 positive esophagus squamous cell carcinoma sensitive Cisplatin + Fluorouracil + Pembrolizumab Phase III Actionable In a Phase III trial (KEYNOTE-590), addition of Keytruda (pembrolizumab) to cisplatin and fluorouracil significantly improved overall survival (13.9 vs 8.8 mo, HR=0.57, p<0.0001) and progression-free survival (6.3 vs 5.8 mo, HR=0.65, p<0.0001) in patients with metastatic or locally advanced esophageal squamous cell carcinoma expressing PD-L1 (CPS>=10) (Ann Oncol. 31, no. 4_suppl (Sep 2020) S1192-S1193; NCT03189719). detail...
CD274 positive gastroesophageal junction adenocarcinoma sensitive Cisplatin + Fluorouracil + Pembrolizumab Phase III Actionable In a Phase III trial (KEYNOTE-590), addition of Keytruda (pembrolizumab) to cisplatin and fluorouracil significantly improved overall survival (13.5 vs 9.4 mo, HR=0.62, p<0.0001) and progression-free survival (7.5 vs 5.5 mo, HR=0.51, p<0.0001) in patients with metastatic or locally advanced esophageal or gastroesophageal junction carcinoma expressing PD-L1 (CPS>=10) (Ann Oncol. 31, no. 4_suppl (Sep 2020) S1192-S1193; NCT03189719). detail...
CD274 positive esophageal carcinoma sensitive Cisplatin + Fluorouracil + Pembrolizumab Phase III Actionable In a Phase III trial (KEYNOTE-590), addition of Keytruda (pembrolizumab) to cisplatin and fluorouracil significantly improved overall survival (13.5 vs 9.4 mo, HR=0.62, p<0.0001) and progression-free survival (7.5 vs 5.5 mo, HR=0.51, p<0.0001) in patients with metastatic or locally advanced esophageal or gastroesophageal junction carcinoma expressing PD-L1 (CPS>=10) (Ann Oncol. 31, no. 4_suppl (Sep 2020) S1192-S1193; NCT03189719). detail...