[ESMO 2024] Death Risk Reduced by 34% Using Keytruda for Previously Untreated 'Samjung Eumseong' Breast Cancer

MSD Immuno-oncology Drug 'Keytruda' Announces 'KEYNOTE-522' for Breast Cancer Perioperative Therapy at ESMO

'Targeted Therapy' Lacking Targets in Triple-Negative Breast Cancer
Difficult to Treat and Aggressive Prognosis
Survival Improvement Observed with Keytruda Use

MSD's blockbuster immuno-oncology drug Keytruda has demonstrated therapeutic efficacy for a rare type of breast cancer that previously had no treatment options, presenting new possibilities.

Professor Peter Schmidt of the Barts Cancer Institute in London, UK, is presenting the overall survival results of the Phase 3 KEYNOTE-522 study on the third day of the 2024 European Society for Medical Oncology (ESMO) conference held in Barcelona, Spain, on the 15th (local time). The study focuses on neoadjuvant therapy with Keytruda and chemotherapy followed by adjuvant therapy for high-risk early triple-negative breast cancer.
[Photo by Lee Chunhee]

On the third day of the 2024 European Society for Medical Oncology (ESMO) conference held in Barcelona, Spain, Professor Peter Schmid of the Barts Cancer Institute in London, UK, presented the "Overall Survival Results of the Phase 3 KEYNOTE-522 Study: Neoadjuvant Therapy with Keytruda Plus Chemotherapy and Adjuvant Therapy After Surgery for High-Risk Early Triple-Negative Breast Cancer" on the 15th (local time). He emphasized the superiority of Keytruda in breast cancer treatment, stating, "These study results enable this regimen to be used as the standard treatment for patients with high-risk early triple-negative breast cancer."

The triple-negative breast cancer targeted in this study refers to cases where none of the three receptors?human epidermal growth factor receptor 2 (HER2), estrogen receptor, and progesterone receptor?commonly targeted in breast cancer therapies, are present. In other words, these patients cannot benefit from targeted therapies or hormone treatments.

Because of this, triple-negative breast cancer is not only difficult to treat but is also considered aggressive in its progression. Currently, breast cancer has a 5-year survival rate of 99% at the localized stage and 31% even when it has metastasized to other areas. However, for triple-negative breast cancer, these rates drop to 91% and 12%, respectively.

Moreover, triple-negative breast cancer occurs in 15-20% of all breast cancer patients and has a higher incidence in premenopausal younger women, with 36.6% of patients under 50 years old compared to 24.4% in other breast cancer types. Since younger patients face longer periods of fear regarding recurrence and metastasis as well as anxiety about treatment, this cancer poses a significant risk of reduced quality of life.

MSD's immuno-oncology drug Keytruda

Despite its high risk, the introduction of the immuno-oncology drug Keytruda for triple-negative breast cancer has opened new avenues. The KEYNOTE-522 regimen combines Keytruda with chemotherapy before surgery to reduce tumor size in high-risk patients with tumors larger than 2 cm, followed by additional Keytruda treatment after surgery to enhance therapeutic effects. Additionally, the KEYNOTE-355 regimen, conducted on patients with unresectable recurrent or metastatic disease, has also been approved domestically after demonstrating efficacy.

Among these, the KEYNOTE-522 regimen is already recommended as the first-line treatment for high-risk early triple-negative breast cancer patients by organizations such as the National Comprehensive Cancer Network (NCCN) in the United States. However, despite more than 2,000 patients having been treated with this regimen since its approval in July 2022 in Korea, it has yet to be covered by national health insurance.

The recent release of the first overall survival data for this regimen drew attention. After observing patients for up to 7 years, 115 out of 784 patients (14.7%) in the Keytruda group died, compared to 85 out of 390 patients (21.8%) in the control group. The hazard ratio was 0.66, indicating that using Keytruda reduced the risk of death by 34%. When observed up to 5 years, the death rates were 13.4% and 18.3%, respectively.

A notable point in the presentation was that Keytruda was particularly effective in patients who did not achieve pathological complete response (pCR), meaning the cancer was not completely eradicated after surgery. For patients whose cancer was completely removed by surgery, the 5-year survival rates were 95.1% in the Keytruda group and 94.4% in the placebo group, showing little difference. However, among patients without complete cancer eradication, the rates were 71.8% and 65.7%, respectively, showing a significant gap. However, since randomization was not performed after surgery in the study design, statistical significance was not confirmed. Dr. Marleen Kok from the Netherlands Cancer Institute, who participated as a discussant after the presentation, explained, "In patients without pCR, survival curves diverged depending on whether Keytruda neoadjuvant therapy was used, demonstrating that immunotherapy can alter the tumor microenvironment."

Professor Park Yeon-hee of the Department of Hematology and Oncology at Samsung Seoul Hospital met with reporters immediately after presenting the results of the KEYNOTE-522 study at the 2024 European Society for Medical Oncology (ESMO) on the 15th (local time) to explain the significance of the research.
[Photo by Lee Chun-hee]

Professor Yeonhee Park of the Department of Hematology and Oncology at Samsung Medical Center, who participated in the study, told reporters immediately after the presentation, "This study breaks the stereotype by significantly increasing the cure rate in early-stage patients and extending survival even in non-pCR patients." She also emphasized, "This regimen has a fixed number of doses, so there is no need to worry about whether to continue treatment if it is effective. Medically, neoadjuvant therapy enhances the effectiveness of immunotherapy."

Professor Park also offered suggestions regarding the sluggish national health insurance coverage for this regimen in Korea. She stressed the urgency of insurance coverage, saying, "With 5-year overall survival results now available, all the data that can be produced have been produced. Treating triple-negative breast cancer can improve the quality of life for young patients, prevent recurrence, and socially and economically sustain the workforce, thereby saving national finances." She added, "While treatment for stage 4 cancer patients is about living with the disease, early treatment aims for a cure. Saying it is not applicable because it is early-stage is illogical."