First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced esophageal cancer: 5-year outcomes from the phase 3 KEYNOTE-590 study.

250 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 . [Table: see text]