Annals of Oncology 2021 Sep 29
Adjuvant Abemaciclib Combined With Endocrine Therapy for High-Risk Early Breast Cancer: Updated Efficacy and Ki-67 Analysis From the monarchE Study.
Abstract
Background
Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in HR+, HER2-, node-positive, high risk early breast cancer (EBC) at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome (PO) analysis and an additional follow-up analysis (AFU1).
Patients and methods
This global, phase 3, open-label trial, randomized (1:1) 5637 patients to adjuvant ET for ≥5 years +/- abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALN), or 1-3 positive ALN and either Grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALN and centrally determined high Ki-67 index (≥20%). Primary endpoint was IDFS in the intent-to-treat population (Cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety.
Results
At the PO analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event (HR=0.71, 95% CI: 0.58, 0.87; nominal p=0.0009). At the AFU1 analysis, with 27 months median follow-up and 90% of patients off-treatment, IDFS (HR=0.70, 95% CI=0.59, 0.82; nominal p<0.0001) and DRFS (HR=0.69, 95% CI=0.57, 0.83; nominal p<0.0001) benefit was maintained. The absolute improvement in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. While Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data was consistent with the known abemaciclib risk profile.
Conclusion
Abemaciclib+ET significantly improved IDFS in patients with HR+, HER-, node-positive, high risk EBC, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.
Related Questions
What factors do you use to decide between ribociclib and abemaciclib for high risk HR+/HER2− early breast cancer?
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Would you hold abemaciclib during adjuvant chest wall/axillary radiation after mastectomy?
I agree. There are some concerns that put cells into cell cycle arrest may also impact the benefits of radiation therapy. So it is recommended to hold abemaciclib during radiation therapy.
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This is a great question and I hope we eventually have data to guide us. I also do not know how insurers will handle these types of requests. This high-risk ER+ population has a 10-year risk of distant recurrence between 20 to 40% with continued risk of recurrence over 20 years based on the EBCTCG d...
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Is there a role for adjuvant capecitabine in sequence with abemaciclib for high risk HR+ breast cancer with residual disease?
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Would you still obtain Ki-67 prior to use of adjuvant abemaciclib in a patient who has otherwise met MonarchE treatment criteria, such as 1-3 positive LNs, grade 3 and/or tumor >5 cm?
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Should we be performing sentinel lymph node biopsies for HR+ patients ≥70 years of age?
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Does the magnitude of benefit with 2 years of adjuvant abemaciclib outweigh side effects, given that many patients will receive CDK 4/6 inhibitors at breast cancer recurrence, precluding OS benefits?
In terms of balancing benefit in terms of risk reduction of cancer recurrence versus adverse events, this is always an important consideration in introducing a novel therapy. In patients who are at high risk based on the criteria for the trial, namely node positive based on more than 4 nodes or if 1...
If you have a high risk HR+, BRCA+ breast cancer patient who qualifies for adjuvant olaparib and abemaciclib, which one would you give and why?
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How and on which specimens will you perform Ki-67 testing in newly diagnosed breast cancer?
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How far can you dose reduce abemaciclib for a patient who is having toxicity at starting doses?
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Will you offer adjuvant abemaciclib to breast cancer patients with high Ki-67 who are unable to receive either neoadjuvant or adjuvant chemotherapy due to comorbidities or who decline chemotherapy?
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