Key Points:
- A four-year analysis of Phase 3 monarchE trial found continued efficacy of abemaciclib plus standard endocrine therapy
- Adjuvant abemaciclib increased both invasive disease free survival and distant relapse-free survival compared to endocrine therapy alone.
- Invasive disease free survival was 6.4% in the abemaciclib plus endocrine therapy group vs endocrine therapy alone (85.8% and 79.4%, respectively).
High-risk early breast cancer patients who are candidates for adjuvant abemaciclib with endocrine treatment are being studied in the monarchE study, a randomized, open-label, phase 3 trial. Patients in this study had to have hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive breast cancer, and they were randomly assigned (1:1) to receive either standard-of-care endocrine therapy of the physician’s choice for up to 10 years with or without abemaciclib 150 mg orally twice a day for 2 years (treatment period). Overall survival, distant relapse-free, and invasive disease-free survival at longer follow-up were reviewed as parameters during this interim analysis.
The results verified that the combination of abemaciclib and endocrine treatment significantly increased both invasive disease-free survival and distant relapse-free survival compared to endocrine therapy alone. An additional 42 months of follow-up confirmed the previously observed improvement in invasive disease-free survival (HR 0.664, 95% CI 0.578-0.762, nominal p<0.0001). When comparing the two groups’ invasive disease-free survival rates after 4 years, the abemaciclib plus endocrine treatment group came out on top (85.8% [95% CI 84.2-87.3]) by a margin of 6.4% (79.4% [77.5-81.1]).
At 4 years, there was no statistically significant difference in overall survival between the two groups: 157 (5.6%) of 2808 patients in the abemaciclib plus endocrine therapy group died, compared with 173 (6.1%) of 2829 patients in the endocrine therapy alone group (HR 0.929, 95% CI 0.748-1.153; p=0.50).
Neutropenia (548 [19.6] of 2791 patients receiving abemaciclib plus endocrine therapy vs. 24 [0.9%] of 2800 patients in the endocrine therapy alone group), leukopenia (318 [11.4] vs. 11 [0.4%]), and diarrhea (218 [7.8] vs. six [0.2%]) were the most common grade 3-4 adverse events in the combination group. Patients receiving abemaciclib with endocrine treatment were more likely to have serious adverse events (433/15.5% vs. 256/91%, respectively) than those getting endocrine therapy alone (281/91% vs. 2800/9%). Abemaciclib with endocrine therapy led to two deaths (from diarrhea and pneumonitis, respectively), but endocrine therapy alone resulted in no fatalities.
Taking abemaciclib as an adjuvant therapy may help lower the chance of recurrence, according to the results of this interim analysis. Further supporting the use of abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer was the benefit sustained even after treatment completion with an absolute increase at 4 years. More research into the use of abemaciclib with endocrine therapy for the treatment of patients is required to establish improvement in overall survivability.
Source:https://pubmed.ncbi.nlm.nih.gov/36493792/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03155997
Johnston SRD, Toi M, O’Shaughnessy J, Rastogi P, Campone M, Neven P, Huang CS, Huober J, Jaliffe GG, Cicin I, Tolaney SM, Goetz MP, Rugo HS, Senkus E, Testa L, Del Mastro L, Shimizu C, Wei R, Shahir A, Munoz M, San Antonio B, André V, Harbeck N, Martin M; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Jan;24(1):77-90. doi: 10.1016/S1470-2045(22)00694-5. Epub 2022 Dec 6. PMID: 36493792.
