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Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: The phase 3 KEYNOTE-590 study
Kato, K. Sun, J. M. Shah, M. A. Enzinger, P. C. Adenis, A. Doi, T. Kojima, T. Metges, J. P. Li, Z. Kim, S. B.
Kato, K.
Sun, J. M.
Shah, M. A.
Enzinger, P. C.
Adenis, A.
Doi, T.
Kojima, T.
Metges, J. P.
Li, Z.
Kim, S. B.
Citations
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Abstract
Background: KEYNOTE-590 (NCT03189719) is a randomized, international, doubleblind
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.
Description
Date
2020
Publisher
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Keywords
Type
Meetings and Proceedings
Citation
Kato K, Sun JM, Shah MA, Enzinger PC, Adenis A, Doi T, et al. LBA8_PR Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: The phase 3 KEYNOTE-590 study. Annals of Oncology. 2020;31:S1192-S3.