KEY TAKEAWAYS
- The KEYNOTE-590 phase III trial aimed to evaluate 5-yr survival for 1L pembro + chemo vs. pbo + chemo in advanced esophageal cancer patients.
- The primary endpoints were OS in ESCC with PD-L1 CPS ≥10 and OS/PFS per RECIST v1.1 in all ESCC patients.
- The results demonstrated lasting effectiveness of pembro+ chemo without new safety issues, supporting its 1L use.
In the randomized phase 3 KEYNOTE-590 study, first-line pembrolizumab (pembro) plus chemotherapy (chemo) notably enhanced survival compared to placebo (pbo) plus chemo in patients with advanced esophageal cancer over a median follow-up of 22.6 months.
To report the 5-year follow-up data, Manish A. Shah and the team spearheaded the study that aimed to evaluate the efficacy of first-line (1L) pembro plus chemo versus pbo plus chemo in advanced esophageal cancer patients.
The study included patients who had locally advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus (ESCC), or Siewert type I gastroesophageal junction adenocarcinoma. They were required to have measurable disease according to RECIST v1.1 criteria and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. Patients were randomized in a 1:1 ratio to receive either pembro 200 mg or pbo intravenously every 3 weeks for up to 35 cycles, both in combination with chemo (5-fluorouracil for up to 35 cycles and cisplatin for up to 6 cycles).
The primary endpoints included overall survival (OS) in patients with ESCC and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10, as well as OS and progression-free survival (PFS) according to RECIST v1.1 criteria assessed by the investigator in all patients, patients with ESCC regardless of PD-L1 status, and patients in the intention-to-treat (ITT) population with CPS ≥10. Secondary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST v1.1 criteria assessed by the investigator, along with safety measures. Patient-reported outcomes were also collected.
About 749 patients were randomized of which 373 received pembro plus chemo, and 376 received pbo plus chemo. The median follow-up time was 58.8 months (range, 49.2-70.6). Among 740 evaluable patients, 701 (94.7%) discontinued treatment, primarily due to disease progression (449 patients; 60.7%). The ORR and DOR were reported. In the ITT population, median OS was 12.3 months with pembro plus chemo and 9.8 months with pbo plus chemo (HR 0.72 [95% CI 0.62-0.84]).
The 5-year OS rates were 10.6% and 3.0%, respectively. The median PFS was 6.3 months with pembro plus chemo and 5.8 months with pbo plus chemo (HR 0.64 [95% CI 0.54-0.75]); 5-year PFS rates were 5.5% and 0%, respectively. Grade 3-5 treatment-related adverse events (TRAEs) occurred in 266 patients (71.9%) in the pembro plus chemo arm and 250 patients (67.6%) in the pbo plus chemo arm. Treatment-related AEs led to death in 9 patients (2.4%) and 5 patients (1.4%) in the pembro plus chemo and pbo plus chemo arms, respectively.
The study concluded that after 5 years, the use of pembro plus chemo exhibited enduring efficacy compared to placebo plus chemo in untreated advanced esophageal cancer patients. Additionally, no new safety concerns emerged, reaffirming the long-term support for first-line pembro plus chemo in this setting. Research was funded by Merck Sharp & Dohme LLC
Source: https://meetings.asco.org/abstracts-presentations/229140
Clinical Trial: https://clinicaltrials.gov/study/NCT03189719
Shah MA, Sun JM, Shen L, et al. (2024). “First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced esophageal cancer: 5-year outcomes from the phase 3 KEYNOTE-590 study.” Presented at ASCO GI 2024 10.1200/JCO.2024.42.3_suppl.250 (250).
