Longer follow-up supports benefit of abemaciclib for high-risk breast cancer
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SAN ANTONIO — The benefit of adding abemaciclib to adjuvant endocrine therapy for certain patients with high-risk breast cancer deepened with time, according to randomized phase 3 results presented at San Antonio Breast Cancer Symposium.
A pre-planned interim analysis of the monarchE trial — which included patients with hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer — showed increases in absolute improvement in invasive DFS and distant RFS benefit at 4 years compared with 2- and 3-year estimates.
“These data further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer,” Stephen Johnston, MA, PhD, FRCP, head of medical oncology and head of the breast unit at The Royal Marsden NHS Foundation Trust, said during a presentation.
Abemaciclib (Verzenio, Eli Lilly) — a cyclin-dependent kinase (CDK) 4/6 inhibitor — is approved for use by patients with advanced breast cancer or with hormone receptor-positive, HER2-negative breast cancer in combination with endocrine therapy.
In the international monarchE study, Johnston and colleagues assessed abemaciclib in the adjuvant setting among 5,637 men and women with hormone receptor-positive, HER2-negative early-stage breast cancer at high risk for relapse.
Researchers defined high risk as four or more positive axillary lymph nodes, or one to three positive axillary lymph nodes with either grade 3 disease or tumor size of at least 5 cm (n = 5,120). A second cohort included 517 patients with one to three positive axillary lymph nodes and central Ki-67 index of 20% or greater.
Investigators randomly assigned patients to for up to 10 years with or without 150 mg abemaciclib twice daily for 2 years.
Invasive DFS served as the primary endpoint, and distant RFS, OS and safety served as secondary endpoints.
Prior results showed statistically significant improvement in invasive DFS and distant RFS in the abemaciclib group.
At SABCS, Johnston presented findings from a prespecified OS interim analysis planned to occur 2 years after the primary outcome analysis.
After median follow-up of 42 months, all patients had finished abemaciclib treatment.
Results showed a durable benefit with abemaciclib with regard to invasive DFS (85.8% vs. 79.4%; HR = 0.66; 95% CI, 0.57-0.76).
Researchers observed continued separation of the invasive DFS curves, with a larger absolute benefit in invasive DFS rate at 4 years (6.4%) than at 3 years (absolute difference, 4.8%) or 2 years (absolute difference, 2.8%).
The benefit in invasive DFS appeared consistent across all prespecified subgroups.
Results also showed improved distant RFS at 4 years with abemaciclib (88.4% vs. 82.5%; HR = 0.65; 95% CI, 0.56-0.76). Again, data showed a larger absolute benefit in distant RFS rate at 4 years (5.9%) than at 3 years (4.1%) or 2 years (2.5%).
OS data remained immature; however, researchers observed fewer deaths among patients assigned the combination than those assigned endocrine therapy alone (5.6% vs. 6.1%; HR = 0.92; 95% CI, 0.74-1.15). This finding suggests “a survival signal favoring abemaciclib is emerging,” Johnston and colleagues wrote.
Consistent with prior reports, Ki-67 index of 20% or higher appeared associated with poorer prognosis; however, abemaciclib treatment conferred similar outcomes regardless of patients Ki-67 index.
Updated safety findings appeared consistent with previous analyses, Johnston said. Adverse events that occurred more frequently among abemaciclib-treated patients than those assigned endocrine therapy alone included diarrhea (84% vs. 9%), fatigue (41% vs. 18%), neutropenia (46% vs. 6%), leukopenia (38% vs. 7%), abdominal pain (36% vs. 10%) and nausea (30% vs. 9%).
Eighteen percent of patients discontinued abemaciclib due to adverse events.
“The majority of adverse events occurred early in patients on study,” Johnston said. “They were managed by appropriate dose holds and dose reductions, which were common in the study to allow patients to stay on for the 2-year treatment period.”
Perspective
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Azka Ali, MD
The clinical benefit of the addition of abemaciclib for 2 years to adjuvant endocrine therapy for patients with early high-risk, node-positive, hormone receptor-positive breast cancer had been shown in the phase 3 MonarchE trial. Abemaciclib, a CDK inhibitor, is approved for use in advanced hormone receptor-positive, HER2-negative breast cancer. This year’s San Antonio Breast Cancer Symposium featured a 4-year update of results. At a 42-month follow up, researchers reported a 33.6% improvement in invasive DFS. OS data remained immature but fewer deaths had been observed in the abemaciclib group. Additionally, fewer patients with metastatic disease were noted in the abemaciclib arm. No additional safety signals had been noted.Abemaciclib continues to be an active agent in high-risk, hormone receptor-positive breast cancer, and its benefit remains clinically meaningful. Patients meeting the high-risk criteria as defined in the MonarchE trial should be offered adjuvant abemaciclib. We look forward to seeing its ongoing benefit as the data matures in the years to follow.
It must be noted that there were 61.7% dose holds, 43.6% dose reductions and 18.5% dose discontinuations in the abemaciclib arm. Although therapies are becoming more effective, the best therapies are the ones our patients can tolerate, so we must continue to identify early toxicities among our patients, with aggressive mitigation strategies with supportive care and dose reductions.
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Johnston S, et al. Abstract GS1-09. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2022; San Antonio.
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