Keytruda Improves OS in Stage 4 HER2+ Gastric Cancer

A strong consensus has emerged for the prompt inclusion of Keytruda combination therapy in the reimbursement list, as it is the first treatment to show improved survival rates compared to standard first-line therapy for metastatic HER2-positive gastric cancer.

Gastric cancer, particularly prevalent in East Asia and notably in Korea, is often called the "cancer of Koreans." The disease’s unique heterogeneity makes personalized treatment challenging, with only a 6% survival rate in metastatic cases, underscoring the need for more effective therapies.

A new combination therapy of Keytruda with Herceptin and chemotherapy, approved on December 19, 2023, may replace the standard treatment of Herceptin and chemotherapy. The pivotal Phase 3 KEYNOTE-811 study demonstrated a significant improvement in progression-free survival (PFS), leading to its approval.

For patients with PD-L1-positive expression (CPS ≥1), the Keytruda combination resulted in a median PFS of 10.9 months compared to 7.3 months in the control group, reducing the risk of disease progression or death by 29%.

Although the overall survival (OS) data were initially immature, the final results, presented at the European Society for Medical Oncology (ESMO) on September 14th, confirmed that the combination therapy met all primary efficacy endpoints.

The study results showed that at a median follow-up of 50.2 months, overall survival (OS) in the intent-to-treat (ITT) population was 20.0 months for the Keytruda combination group versus 16.8 months for the Herceptin and chemotherapy group, representing a 20% reduction in the risk of death.

In patients with PD-L1 expression, who comprised approximately 85% of the study population, the Keytruda combination group achieved a median OS of 20.1 months, compared to 15.7 months for the control group—a 21% reduction in the risk of death. Progression-free survival (PFS) for these patients was 10.0 months, versus 7.3 months in the control group, indicating a 28% reduction in the risk of disease progression or death.

In an interview at ESMO, Professor Sun-young Ra emphasized the meaningful improvement in overall survival for gastric cancer patients. She highlighted that the Keytruda combination therapy delivered an objective response rate (ORR) of 76.7%, over 20% higher than the control group, along with notable improvements in progression-free survival. The therapy extended overall survival by approximately four months, providing clinical benefits across all evaluation metrics.

Although not presented at ESMO, there is increasing belief that stage 4 metastatic gastric cancer patients are more likely to improve to a stage where surgery becomes viable with the Keytruda combination, compared to standard treatments.

Professor Ra explained the significance of "conversion surgery," where stage 4 cancer patients improve to the point of being operable. The Keytruda combination therapy not only extends survival but also increases the number of patients eligible for this curative surgery, offering hope for those previously deemed inoperable.

However, she expressed concern that despite the promising data, the therapy has not yet been included in the reimbursement list, limiting access for patients. She stressed the need for prompt reimbursement to ensure the treatment’s availability, citing the compelling overall survival data from the KEYNOTE-811 study as a strong case for inclusion in Korea’s healthcare system.