The introduction of CDK 4/6 inhibitors has changed the treatment paradigm for metastatic breast cancer, addressing previously unmet needs.

The introduction of a new treatment option has been positively evaluated because the existing endocrine therapy, which is used as first-line treatment for HR+/HER2 advanced and metastatic breast cancer, accompanies specific adverse responses, such as thrombosis and musculoskeletal adverse reactions associated with estrogen deprivation.

As CDK4/6 inhibitors have been approved in South Korea, the impact of new treatment options is gradually expanding. During the meeting with Daily Pharm, Dr. Jae Ho Jeong, Professor of the Department of Oncology at Asan Medical Center located in Seoul, stressed the importance of strengthening new drug access to improve treatment settings for HR+/HER2- advanced∙metastatic breast cancer in South Korea.

The number of breast cancer patients in South Korea has been increasing for the past five years, from 2018 to 2023. HR+/HER2- breast cancer type accounts for approximately 60-70% of all metastatic breast cancer.

Currently, the five-year survival rate of patients with early breast cancer is high, at over 90%, but the survival rate of patients with metastatic breast cancer is reported to be very low.

Dr. Jeong said, "Despite the high overall survival rate for breast cancer, the five-year survival rate is only 32% when diagnosed as advanced‧metastatic breast cancer." Adding, "Difficult-to-treat cases often include existing multiple metastasis from diagnosis. When patients show resistance to first-line treatment, cancer progression becomes rapid, and patients have poor prognosis."

"Advanced‧metastatic breast cancer has difficult remission and can easily relapse. Thus, the treatment goal is to consider the tumor characteristics, minimize side effects, and extend the progression-free survival (PFS) and overall survival," Dr. Jeong Said. "When establishing a treatment strategy, menopause, cancer progression, internal organ metastasis, and patient's overall health status must be considered."

According to Dr. Jeong, the global guidelines (NCCN, ASCO, ESMO) recommend combination therapy containing endocrine therapy and CDK4/6 inhibitor as a first-line treatment for HR+/HER2- advanced breast cancer. A therapy with CDK4/6 inhibitor is recommended first instead of a cytotoxic anticancer agent for aggressive disease type."

"The introduction of CDK4/6 inhibitors changed a paradigm for HR+/HER2- breast cancer"

Data on CDK4/6 inhibitors for HR+/HER2- breast cancer have been competitively presented.

Kisqali (ribociclib)'s 'RIGHT Choic subgroup study' results presented at the San Antonio Breast Cancer Symposium (SAVCS 2024) have gained attention.

Based on the RIGHT Choice clinical study and the subgroup study, the clinical utility of Kisqali has been confirmed for HR+/HER2- breast cancer patients with internal organ metastasis and aggressive characteristics.

In the study, endocrine therapy in combination with Kisqali demonstrated improved the median progression-free survival (mPFS) in various subtypes of HR+/HER2- advanced metastatic‧breast cancer than a combination therapy with chemotherapy.

Dr. Jeong mentioned regarding this, "When a disease shows aggressive characteristics, chemotherapy, rather than endocrine therapy, is typically widely used in clinical practices. Thus, the results of the RIGHT Choice study hold significant importance."

"Breast cancer is not a single type of disease and includes different tumors with various clinical characteristics and show different responses to disease progression and treatments. Depending on these groups, the analysis of the RIGHT Choice study showed that long PFS in the Kisqali combination therapy group," Dr. Jeong said.

Dr. Jeong believes that more studies like these will enable customized treatments, allowing patients to receive appropriate treatment.

Based on three Phase 3 clinical studies, including the NALEESA-2,3,7 study, Kisqali was confirmed to have consistent improvement to overall survival regardless of menopause status, treatment number, and combined treatment in advanced‧metastasis breast cancer patients. These study results will likely yield synergy.

"Kisqali demonstrated benefits in OS survival through three clinical studies, where the quality of life was maintained and improved, regardless of the existence of combined treatments, the number of treatments, menopause status, metastasis location and number," Dr. Jeong said. "The effectiveness of Kisqali was confirmed in premenopausal patients, extending the treatment paradigm."

"Changes to breast cancer treatment option…time to consider patient access"

In addition to the global clinical study, the efficacy result of Kisqali from the real-world setting in South Korea was presented at the 2024 ESMO ASIA. Likewise, Kisqali's effect has been demonstrated in clinical settings.

Dr. Jeong explains that no significant safety-related issues have not been reported for Kisqali, other than general side effects like fatigue and rashes, when prescribed. Compared to clinical studies, these side effects are manageable.

"Considering a high percentage of premenopausal patients, Kisqali offers a benefit for use regardless of the menopause status. Effects and safety of Kisqali were demonstrated in these patient groups, and it has become a new standard therapy," Dr. Jeong said.

"Furthermore, Kisqali has the advantage of increasing patient adherence because it offers convenience in dosage changes and administration guidance," Dr. Jeong said. "It is possible to change the dosage with the same formulation by changing the number of tablets. Given that a system to reduce re-purchase burden when changing a dosage has been introduced, the drug is gaining a positive review in clinical settings."

However, Dr. Jeong says that expanded reimbursement standard is crucial to ensure patients to benefit from these new drugs. The introduction of CDK4/6 inhibitors has robustly changed the treatment paradigm for HR+/HER2- advanced‧metastatic breast cancer treatment. Thus, it is necessary to strengthen new drug access.

Dr. Jeong said, "As better treatment options are available for not only HR+/HER2- metastatic breast cancer but also other types of metastatic breast cancer, positive changes have been brought. To improve treatment settings for HR+/HER2- advanced‧ metastatic breast cancer in South Korea, expanded National Health Insurance reimbursement standard and strengthened new drug access are needed."

Ultimately, Dr. Jeong said, "It is important to improve patient access to new treatment options through securing medical facilities and expanding clinical study participation." "Accumulating clinical data that reflects the characteristics of Korean patients is important for establishing a foundation that can influence global guidelines."