Keytruda (pembrolizumab) + trastuzumab and chemotherapy significantly improved overall survival versus trastuzumab and chemotherapy alone in first-line treatment of HER2-positive advanced gastric or GEJ adenocarcinoma

These data are being presented tduring a proffered paper session at the European Society for Medical Oncology (ESMO) Congress 2024 (Presentation #1400O) and are also being simultaneously published in the New England Journal of Medicine .

After a median follow-up of 50.2 months (range, 31.1-64.4), the Keytruda  regimen demonstrated a statistically significant and clinically meaningful improvement in OS in the intention-to-treat (ITT) HER2-positive advanced gastric or GEJ study population, reducing the risk of death by 20% (HR=0.80 [95% CI, 0.67-0.94]; p=0.0040 [p-value bound 0.0201]) compared to trastuzumab and chemotherapy alone. For patients who received the Keytruda regimen, median OS was 20.0 months (95% CI, 17.8-22.1) versus 16.8 months (95% CI, 14.9-18.7) for patients receiving trastuzumab plus chemotherapy alone.

The Keytyruda regimen also demonstrated a clinically meaningful improvement in OS in patients whose tumors expressed PD-L1 (Combined Positive Score [CPS] ?1), reducing the risk of disease progression or death by 21% (HR=0.79 [95% CI, 0.66-0.95]) compared to trastuzumab and chemotherapy alone in these patients. Median OS was 20.1 months (95% CI, 17.9-22.9) for patients with tumors expressing PD-L1 (CPS greater than 1) receiving the Keytruda regimen versus 15.7 months (95% CI, 13.5-18.5) for patients receiving trastuzumab and chemotherapy alone. In the study, 85% of patients’ tumors expressed PD-L1 (CPS  greater than 1).

“The majority of patients with gastric and gastroesophageal cancer are diagnosed at an advanced stage, at which point the five-year survival rate is less than 10%,” said Dr. Yelena Y. Janjigian, chief attending physician, gastrointestinal oncology, Memorial Sloan Kettering Cancer Center, and global lead principal investigator for the KEYNOTE-811 trial. “These overall survival results from the KEYNOTE-811 trial are encouraging and show that adding pembrolizumab to trastuzumab and chemotherapy can extend the lives of certain patients with HER2-positive and PD-L1 positive gastric and gastroesophageal cancer.”

“With these new results, KEYNOTE-811 has met both of its primary endpoints, significantly improving progression-free and overall survival for patients with HER2-positive advanced gastric cancer, with the greatest benefit observed in patients whose tumors express PD-L1 (CPS  greater than 1),” said Dr. M. Catherine Pietanza, vice president, global clinical development, Merck Research Laboratories. “These new survival data add to the strong body of evidence supporting global approvals of this KEYTRUDA-based regimen and underscore the importance of providing promising new treatment options to patients.”

In the U.S., Keytruda, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ?1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Since the FDA’s accelerated approval , the trial has met its dual primary endpoints of progression-free survival (PFS) and OS. These results have been shared with regulatory authorities worldwide.

In August 2023, the European Commission (EC) approved Keytruda in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma in adults whose tumors express PD-L1 (CPS greater than ?1) based on PFS results from KEYNOTE-811.