Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Ref Type

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.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

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	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...
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...