Editor’s Note: At the recent ESMO-ASIA Congress, Professor Takayuki delivered an in-depth interpretation of the latest follow-up data from the Asian subgroup of the KEYNOTE-859 study. The presentation explored the long-term clinical value of pembrolizumab plus chemotherapy as a first-line treatment for Asian patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, providing a comprehensive look at the regimen's durable efficacy over a 5-year timeframe. 01. Evidence Consistency: Robust Proof of Benefit in the Asian Population
Addressing historical concerns regarding potential “false-positive” benefits of first-line immunotherapy combined with chemotherapy in Asian populations, Professor Takayuki provided a definitive rebuttal through the analysis of forest plots from multiple studies. Currently, subgroup analyses from three large-scale global clinical trials consistently demonstrate a clear trend toward improved outcomes when immune checkpoint inhibitors (ICIs) are added to chemotherapy in Asian participants compared to non-Asian cohorts.
Furthermore, a meta-analysis conducted this year by South Korean researchers—incorporating 5 Asian and 8 global studies—further confirmed that first-line ICI combination therapy yields sustained and stable clinical benefits specifically in Asian populations. This consistency across studies and populations solidifies the foundational role of immuno-combination regimens in the treatment of advanced gastric cancer in Asia.
02. KEYNOTE-859 Data Update: A Leap to 58.4 Months of Follow-up
KEYNOTE-859 is a global, multicenter, randomized, double-blind Phase III clinical trial designed to evaluate pembrolizumab plus chemotherapy versus placebo plus chemotherapy as a first-line treatment for HER2-negative advanced G/GEJ adenocarcinoma.
While preliminary data from the Asian subgroup had previously been presented at the ESMO GI Congress with a median follow-up of 41.6 months, the current meeting provided updated results from a significantly extended period. With a median follow-up now reaching 58.4 months, the pembrolizumab combination regimen continued to demonstrate comprehensive maintenance of benefits in Overall Survival (OS), Progression-Free Survival (PFS), and Objective Response Rate (ORR) among Asian patients.
03. Long-term Survival Breakthrough: Three-Year Survival Rates Reach New Heights
Regarding clinical prognostic indicators, the core highlight of this update is the remarkable improvement in long-term survival. Data showed that at the three-year (36-month) landmark, approximately one-quarter (25%) of Asian patients with advanced G/GEJ adenocarcinoma remained alive.
Professor Takayuki emphasized that this proportion represents a milestone in clinical practice for this aggressive disease. Given the heterogeneity of gastric cancer, this survival rate is expected to be even higher in patients with an elevated PD-L1 Combined Positive Score (CPS). This indicates that pembrolizumab plus chemotherapy not only induces early remission but also translates into a durable, long-term survival advantage.
04. Safety Assessment: No New Toxicity Signals
As the follow-up period extended toward 5 years, the long-term safety profile of the regimen became a focal point of clinical interest. The updated data revealed no new toxicity signals in the pembrolizumab plus chemotherapy group during the 58.4-month observation period. These results prove that the combination regimen maintains long-term efficacy while remaining well-tolerated and safe, meeting the rigorous requirements for long-term first-line treatment of advanced gastric cancer.
Conclusion and Outlook
The long-term follow-up data from the KEYNOTE-859 Asian subgroup strongly support pembrolizumab plus chemotherapy as the standard first-line regimen for advanced gastric cancer in Asia. Professor Takayuki concluded that whether considering the consistency of benefit observed in forest plots or the robust 58.4-month survival data, the addition of ICIs significantly improves patient prognosis. Moving forward, precision screening and individualized therapy for populations with high CPS scores will further optimize the first-line treatment landscape for Asian gastric cancer patients.
