Meeting
2024 ASCO Gastrointestinal Cancers Symposium
First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced esophageal cancer: 5-year outcomes from the phase 3 KEYNOTE-590 study.
Authors
Manish A. Shah
Weill Cornell Medical College, New York, NY
Manish A. Shah , Jong-Mu Sun , Lin Shen , Ken Kato , Peter C. Enzinger , Antoine Adenis , Toshihiko Doi , Takashi Kojima , Zhigang Li , Sung-Bae Kim , Byoung Chul Cho , Wasat Mansoor , Shau-Hsuan Li , Patrapim Sunpaweravong , Maria Alsina Maqueda , Gary L Buchschacher Jr., Jimin Wu , Sukrut Shah , Pooja Bhagia , Jean-Philippe Metges
Organizations
Weill Cornell Medical College, New York, NY, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Peking University Cancer Hospital & Institute, Beijing, China, National Cancer Center Hospital, Tokyo, Japan, Dana-Farber Cancer Institute, Boston, MA, IRCM, Université Montpellier, ICM, Montpellier, France, National Cancer Center Hospital East, Kashiwa, Japan, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, The Christie NHS Foundation Trust, Manchester, United Kingdom, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Prince of Songkla University Hospital, Songkhla, Thailand, Vall d’Hebron Institute of Oncology, Barcelona, Spain, Kaiser Permanente Southern California, Los Angeles Medical Center, Los Angeles, CA, Merck & Co., Inc., Rahway, NJ, CHU Brest–Institut de Cancerologie et d’Hematologie ARPEGO Network, Brest, France
Research Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Background: First-line (1L) pembro + chemo significantly improved survival versus placebo (pbo) + chemo in patients (pts) with advanced esophageal cancer after a median follow-up of 22.6 mo in the randomized phase 3 KEYNOTE-590 study (NCT03189719). We report 5-yr follow-up data. Methods: Eligible pts had locally advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus (ESCC), or Siewert type I gastroesophageal junction adenocarcinoma; measurable disease per RECIST v1.1; and ECOG PS 0 or 1. Pts were randomized 1:1 to receive pembro 200 mg or pbo IV every 3 weeks for ≤35 cycles both with chemo (5-fluorouracil [≤35 cycles] and cisplatin [≤6 cycles]). Primary end points were OS in pts with ESCC and PD-L1 CPS ≥10 and OS and PFS per RECIST v1.1 by investigator in all pts, pts with ESCC regardless of PD-L1, and pts in the ITT population with CPS ≥10. Secondary end points included ORR and DOR per RECIST v1.1 by investigator and safety. Pt-reported outcomes will also be presented. Data cutoff was July 10, 2023. Results: Overall, 749 pts were randomized to receive pembro + chemo (n = 373) or pbo + chemo (n = 376). Median time from randomization to data cutoff was 58.8 mo (range, 49.2-70.6). A total of 701/740 pts (94.7%) discontinued treatment; most commonly due to progressive disease (n = 449; 60.7%). ORR and DOR by pt population are provided (Table). In the ITT population, median OS was 12.3 mo for pembro + chemo and 9.8 mo for pbo + chemo (HR 0.72 [95% CI 0.62-0.84]); 5-yr OS rates were 10.6% and 3.0%, respectively. Median PFS was 6.3 mo for pembro + chemo and 5.8 mo for pbo + chemo (HR 0.64 [95% CI 0.54-0.75]); 5-yr PFS rates were 5.5% and 0%, respectively. Grade 3-5 treatment-related AEs occurred in 266 (71.9%) pts in the pembro + chemo arm and 250 (67.6%) pts in the pbo + chemo arm. Treatment-related AEs led to death in 9 (2.4%) and 5 (1.4%) pts in the pembro + chemo and pbo + chemo arms, respectively. Conclusions: After 5 yrs, use of pembro + chemo showed durable efficacy versus pbo + chemo, with no new safety concerns in pts with untreated advanced esophageal cancer. Long-term results continue to support 1L pembro + chemo for advanced esophageal cancer. Clinical trial information: NCT03189719.
| OS and PFS | ITT n = 749 | ESCC n = 548 | CPS ≥10 n = 383 | ESCC and CPS ≥10 n = 286 |
|---|---|---|---|---|
| OS, median, HR (95% CI)a,b | 0.72 (0.62-0.84) | 0.71 (0.60-0.85) | 0.64 (0.52-0.80) | 0.60 (0.46-0.76) |
| 5-yr OS rate,a,b % | 10.6 vs 3.0 | 11.8 vs 3.4 | 12.8 vs 3.8 | 13.8 vs 3.7 |
| PFS, median, HR (95% CI)a,b,c | 0.64 (0.54-0.75) | 0.65 (0.54-0.78) | 0.51 (0.40-0.64) | 0.53 (0.41-0.69) |
| ORR,b,c % | 45.0 vs 29.3 | 43.8 vs 31.0 | 51.1 vs 26.9 | 51.0 vs 28.0 |
| DOR,a,b,c median, mo (range) | 8.3 (1.2+ to 65.9+) vs 6.0 (1.5+ to 31.1) | 9.1 (1.2+ to 65.9+) vs 6.1 (1.5+ to 31.1) | 10.4 (1.9 to 65.9+) vs 5.6 (1.5+ to 31.1) | 10.4 (2.2+ to 65.9+) vs 4.4 (1.5+ to 31.1) |
NR, not reached.
aKaplan-Meier estimate.
bData are for pembro + chemo vs pbo + chemo.
cPer RECIST v1.1 by investigator review.
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Abstract Details
Session Type
Rapid Oral Abstract Session
Session Title
Rapid Oral Abstract Session A: Cancers of the Esophagus and Stomach
Track
Esophageal and Gastric Cancer,Other GI Cancer
Sub Track
Therapeutics
Clinical Trial Registration Number
NCT03189719
Citation
J Clin Oncol 42, 2024 (suppl 3; abstr 250)
DOI
10.1200/JCO.2024.42.3_suppl.250
Abstract #
250
Abstract Disclosures
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