[ESMO 2024] 'World's Best-Selling Drug' Keytruda Extends Survival in Advanced Stomach Cancer Patients

Final Results of 'KEYNOTE-811' Clinical Study on Keytruda Combination Therapy for HER2-Positive Gastric Cancer

Confirmed Efficacy Surpassing Existing Standard Treatments in Late-Stage Gastric Cancer Patients with 5-Year Survival Rate Dropping to 6%

Leveraging its characteristic as an immune checkpoint inhibitor, MSD's Keytruda, which has demonstrated efficacy in dozens of types of cancer and secured the throne as the 'world's top-selling pharmaceutical,' presented new possibilities by proving its therapeutic efficacy in advanced gastric cancer?a condition with high unmet needs?at the 2024 European Society for Medical Oncology (ESMO) Congress.

Dr. Sara Ronardi from the Veneto Oncology Institute in Italy is presenting the final follow-up results of the 'KEYNOTE-811' clinical trial of Keytruda for HER2-positive gastric cancer patients on the second day of the 2024 European Society for Medical Oncology (ESMO) conference held in Barcelona, Spain, on the 14th (local time).
[Photo by Lee Chunhee]

Dr. Sara Lonardi from the Veneto Institute of Oncology in Italy emphasized the superiority of Keytruda in gastric cancer treatment during her presentation on the second day of the 2024 ESMO Congress held in Barcelona, Spain, on the 14th (local time). She discussed the "final overall survival results of the phase 3 KEYNOTE-811 study on Keytruda combined with trastuzumab (Herceptin) and chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric cancer," stating, "This clinical data confirms Keytruda combination therapy as the standard first-line treatment for patients with unresectable or metastatic HER2-positive gastric cancer expressing programmed cell death protein 1 ligand (PD-L1)."

Keytruda is considered a blockbuster drug, ranking first in global pharmaceutical sales last year with $25.011 billion (approximately 33 trillion KRW) in revenue. Capitalizing on its advantage as an immune checkpoint inhibitor, it continues to expand its therapeutic scope by demonstrating efficacy in dozens of cancer types, including lung cancer and head and neck cancer, in addition to gastric cancer.

Keytruda treats cancer by neutralizing the fake pass that cancer cells use to deceive the body's immune system. Cancer cells produce a protein called PD-L1 to prevent immune cells, specifically T cells, from attacking them. When PD-L1 binds to the PD-1 protein on T cells, the T cells fail to recognize cancer cells as enemies and cannot attack them. However, Keytruda binds first to the PD-1 protein on T cells, neutralizing this interaction and enabling T cells to recognize and attack cancer cells normally. Because it interferes with the binding between T cells and cancer cells, it is effective against various cancers. It has been approved for 17 cancer types domestically.

MSD's immuno-oncology drug Keytruda

Among these, gastric cancer?the subject of this study?is so prevalent in East Asia, including Korea, that it is often called the "cancer of Koreans." Korea's national cancer screening program facilitates easy access to gastroscopy, leading to increased early detection and continuous improvement in mortality rates. However, if detection is delayed, the survival rate still drops sharply. When cancer progresses to the advanced or metastatic stage, where it penetrates the stomach lining and spreads to other areas (terminal stage), the 5-year survival rate falls to about 6%. Approximately 95 out of 100 patients diagnosed at this stage do not survive beyond five years.

Currently, HER2 is the only target used as a targeted therapy for gastric cancer. Cancer cells produce various mutations, including PD-L1 and HER2, to survive, with HER2 mutations observed in 15-20% of gastric cancer patients. Although the combination of trastuzumab targeting HER2 with chemotherapy has become the standard treatment, this regimen was introduced about 15 years ago, leaving significant unmet needs for new therapies.

In this context, domestic researchers Dr. Sunyoung Ra and Dr. Hyunchul Jung from Yonsei Cancer Hospital's Department of Oncology introduced Keytruda combination therapy, presenting new possibilities. A small-scale investigator-initiated clinical trial called PANTHERA, involving 43 HER2-positive gastric cancer patients in Korea, confirmed the potential to extend patient survival. Similar clinical results from the United States led MSD to initiate the large-scale phase 3 KEYNOTE-811 trial involving a total of 698 patients.

Dr. Sara Ronardi from the Veneto Oncology Institute in Italy is presenting the final follow-up results of the 'KEYNOTE-811' clinical trial of Keytruda for HER2-positive gastric cancer patients on the second day of the 2024 European Society for Medical Oncology (ESMO) conference held in Barcelona, Spain, on the 14th (local time).
[Photo by Lee Chunhee]

The results revealed at this year's ESMO represent the final follow-up data of this study. Previously, follow-up was conducted up to 38.5 months, but this time, results from approximately 4 years (50.2 months) of follow-up were presented. In Korea, based on interim results released last December, Keytruda's indication was expanded. However, it is not yet covered by the National Health Insurance.

In the final study results, among gastric cancer patients positive for both PD-L1 and HER2, the Keytruda combination group showed a median progression-free survival (mPFS) of 10.8 months and a median overall survival (mOS) of 20.1 months, significantly improved compared to the control group's 7.3 months and 15.7 months, respectively. mPFS refers to the median time during which half of the clinical participants survive without cancer progression or recurrence, while mOS indicates the median time half of the participants ultimately survive. Both metrics are key indicators for evaluating anticancer drug efficacy.

The hazard ratios were 0.79 and 0.72, respectively. Adding Keytruda to the existing regimen reduced the risk of cancer progression by 21% and the risk of death by 28%. These figures are similar to previously disclosed interim follow-up results, confirming the stability of the therapeutic effect of Keytruda combination therapy.

On the 14th (local time) at the 2024 European Society for Medical Oncology (ESMO) held in Barcelona, Spain, the final survival study results of the Keynote-811 clinical trial for HER2-positive gastric cancer patients using Keytruda were announced. It was confirmed that adding Keytruda to the existing standard treatment of trastuzumab (Herceptin) combined with chemotherapy increases overall survival (OS) by 3.2 months compared to the placebo group.
[Photo by Lee Chunhee]

Notably, this presentation also revealed, for the first time, overall survival (OS) results for all patients, which had not been disclosed previously due to lack of significant improvement. This clinical trial included 594 patients expressing PD-L1 targeted by Keytruda, as well as 104 PD-L1-negative patients. Previously, results focused only on PD-L1-positive patients. Even among all participants, the Keytruda combination group demonstrated significant improvements with an mPFS of 10.0 months and an mOS of 20.0 months, compared to the placebo combination group's 8.1 months and 16.8 months, respectively. The hazard ratios were 0.80 and 0.73, respectively.