Overall survival (OS) is considered the "gold standard" for evaluating the efficacy of anticancer therapies. However, in early breast cancer, it is also one of the most challenging endpoints to establish due to the long follow-up required.
Verzenio (abemaciclib) has recently addressed this challenge in high-risk, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) early breast cancer, elevating the goal of adjuvant therapy from “preventing recurrence” to “improving survival.”
Paolo Tarantino of the Dana-Farber Cancer Institute presents long-term follow-up results and the clinical significance of OS data for adjuvant abemaciclib at GBCC held at Grand Walkerhill Seoul on April 23. (KBR photo)
At the Global Breast Cancer Conference (GBCC) held on April 23 at the Grand Walkerhill Seoul, Paolo Tarantino of the Dana-Farber Cancer Institute presented under the theme “Optimizing Care in High-Risk HR+/HER2− eBC: Preventing Recurrence and Improving Survival with Adjuvant Abemaciclib.”
The session focused on long-term follow-up results and the clinical significance of OS data for adjuvant therapy combining abemaciclib with endocrine therapy in patients with node-positive, high-risk HR+/HER2− early breast cancer.
Verzenio is a CDK4/6 inhibitor used in combination with endocrine therapy for patients with node-positive, high-risk HR+/HER2− early breast cancer. The pivotal monarchE trial, which enrolled 5,637 patients globally, compared the combination therapy with endocrine therapy alone.
Results showed that patients receiving the combination for two years achieved a seven-year OS rate of 86.4 percent, compared to 84.4 percent in the endocrine therapy-only group—representing a 16.5 percent reduction in the risk of death (HR 0.835). Notably, OS was a prespecified confirmatory endpoint in the study design, rather than a post hoc analysis, underscoring the robustness of the findings.
Beyond numerical differences, these results constitute formal evidence of abemaciclib's survival benefit.
“Survival is the most important outcome for cancer patients,” Dr. Tarantino said. “The combination of abemaciclib and endocrine therapy is the first treatment in over 20 years to clearly improve overall survival compared to a control in the adjuvant setting for early breast cancer.”
He added that demonstrating a meaningful reduction in recurrence risk with a relatively limited two-year treatment period carries important clinical value, as it may ultimately translate into long-term survival benefits.
Early breast cancer is characterized by a persistent risk of recurrence even after surgery and adjuvant therapy. While HR+/HER2− breast cancer is generally considered to have a favorable prognosis, patients with high-risk features—such as lymph node involvement, large tumor size, or high tumor grade—continue to face significant risks of recurrence and distant metastasis.
The session also highlighted that the combination therapy maintained its benefit in reducing the risk of recurrence at the seven-year mark. Sustained separation between treatment groups was observed in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), suggesting long-term durability of benefit.
Tarantino also addressed differences among CDK4/6 inhibitor adjuvant trials. While ribociclib demonstrated meaningful improvement in IDFS in the NATALEE study, he noted that abemaciclib remains the only agent to show statistically significant confirmatory OS data in the intent-to-treat (ITT) population to date.
“The NATALEE study has a relatively shorter follow-up, and its OS data are not yet mature,” he said. “In contrast, the monarchE trial provides a more complete body of evidence, demonstrating reduced mortality risk with nearly seven years of follow-up.”
Some observers also noted that OS data is more significant in the Korean treatment setting. Professor Ahn Jin-hee of the Department of Oncology at Asan Medical Center, who chaired the session, highlighted the importance of data confirming improved survival beyond mere recurrence prevention, citing the age characteristics of domestic breast cancer patients.
“Given the relatively high proportion of breast cancer patients in their 40s and 50s in Korea, the importance of OS—showing that patients actually live longer, not just remain recurrence-free—is even greater,” Professor Ahn said. “The monarchE results, with seven-year follow-up and final OS data, clearly demonstrate the clinical significance of abemaciclib and suggest a major shift in the treatment paradigm for early breast cancer.”
She also noted the rising incidence of breast cancer among women in their 30s and 40s in Korea, emphasizing the broader societal and economic impact of recurrence and metastasis in this population.
“Patients undergoing adjuvant therapy after surgery fear recurrence the most,” Ahn said. “Meaningful OS data can help reduce patient anxiety and encourage a more positive approach to treatment.”
Currently, adjuvant abemaciclib is recommended in both domestic and international guidelines. The Korean Breast Cancer Society recommends its use in combination with endocrine therapy for high-risk patients—defined as those with four or more positive lymph nodes, or one to three positive nodes with tumors ≥5 cm or grade 3 disease—to reduce recurrence risk.
The National Comprehensive Cancer Network (NCCN) also recommends two years of abemaciclib plus endocrine therapy as a Category 1 adjuvant option for high-risk HR+/HER2− breast cancer.
However, reimbursement remains an issue in Korea. While adjuvant abemaciclib is reimbursed in 36 countries—including Japan, China, the United States, the United Kingdom, Germany, Italy, and Australia—it has yet to receive coverage under Korea’s national health insurance system.
Following a reimbursement petition filed last year by the Korean Cancer Study Group’s breast cancer division, the review process is ongoing and is expected to be discussed by the Health Insurance Review and Assessment Service’s Cancer Disease Review Committee.
Dr. Tarantino concluded, “The OS data for abemaciclib reaffirm that two years of combination therapy with endocrine treatment is a standard of care for high-risk early breast cancer. It offers patients new hope by reducing the risk of death.”
He added, “By improving overall survival in HR+/HER2− early breast cancer, abemaciclib has meaningfully altered the long-term disease course. For patients who meet the monarchE criteria, its use should be actively considered.”
Kim Yun-mi
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