Pembrolizumab delivers long-term survival benefits in advanced esophageal cancer

First-line pembrolizumab (pembro) plus chemotherapy (chemo) in patients with untreated advanced esophageal cancer demonstrates robust efficacy after 5 years, with no new safety concerns, when compared with placebo plus chemo, according to a study presented at ASCO GI 2024.

“Long-term results continue to support first-line pembro + chemo for advanced esophageal cancer,” said the researchers led by Manish A Shah from Weill Cornell Medical College, New York, US.

In the randomized phase III KEYNOTE-590 study, first-line pembro + chemo significantly prolonged survival in patients with advanced esophageal cancer relative to placebo after a median follow-up of 22.6 months. Five-year follow-up data were reported in the present study.

Patients with locally advanced or 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 were eligible for analysis. They were randomly assigned to receive either pembro 200 mg or placebo IV every 3 weeks for ≤35 cycles both with chemo.

Primary endpoints were OS in ESCC patients with PD-L1 combined positive score (CPS) ≥10 and OS and progression-free survival (PFS) per RECIST v1.1 by investigators in all patients, patients with ESCC regardless of PD-L1, and those in the intention-to-treat (ITT) population with CPS ≥10. Secondary endpoints were objective response rate (ORR), duration of response (DOR) per RECIST v1.1, and safety.

A total of 749 patients met the eligibility criteria, of whom 373 received pembro + chemo and 376 placebo + chemo. Median time from randomization to data cutoff (10 July 2023) was 58.8 months (range, 49.2‒70.6). Of note, 701 of 740 patients (94.7 percent) ceased treatment mainly due to disease progression (n=449, 60.7 percent). [ASCO GI 2024, abstract 250]

OS and PFS

In the ITT population, patients in the pembro + chemo group had better OS than those in the placebo + chemo group (median OS, 12.3 vs 9.8 months; hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.62‒0.84. At 5 years, OS rates were 10.6 percent and 3.0 percent, respectively.

Median PFS was also better with pembro than with placebo (6.3 vs 5.8 months; HR, 0.64, 95 percent CI, 0.54‒0.75). PFS rates at 5 years were 5.5 percent and 0 percent, respectively.

For the secondary outcomes, ORR in the ITT population was 45.0 percent with pembro + chemo and 29.3 percent with placebo + chemo. Median DOR were 8.3 and 9.1 months, respectively.

In terms of safety, grade 3‒5 treatment-related adverse events (TRAEs) occurred more frequently in the pembro + chemo (n=266, 71.9 percent) than in the placebo + chemo (n=250, 67.6 percent) groups. TRAEs leading to death were also nominally higher in the pembro vs placebo arm (nine vs five patients, 2.4 percent vs 1.4 percent, respectively).

This study was sponsored by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway in New Jersey, US.