36 MONARCH 3: Final Overall Survival Results of Abemaciclib Plus a Nonsteroidal Aromatase Inhibitor as First-Line Therapy for HR+/HER2– Advanced Breast Cancer

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement41st Annual Miami Breast Cancer Conference® - Abstracts
Volume 38
Issue 4
Pages: 40-41

Background

Abemaciclib (abema) is approved both for high-risk early breast cancer as well as advanced breast cancer (ABC) in the first- and second-line setting. In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) significantly improved PFS (HR, 0.540; 95% CI, 0.418-0.698; P = .000002) as initial therapy in hormone receptor–positive, HER2-negative (HR+/HER2–) ABC. Here, we present the final overall survival (OS) analysis of MONARCH 3 (NCT02246621).

Methods

MONARCH 3 is a randomized, double-blind, phase 3 study of abemaciclib plus an NSAI (anastrozole or letrozole) vs placebo plus NSAI in women who are postmenopausal with HR+/HER2– ABC without prior systemic therapy in the advanced setting. OS was a gated secondary end point, and chemotherapy-free survival (CFS) was an exploratory end point. Final OS analysis was planned after about 315 OS events occurred in the intent-to-treat (ITT) population with a split α between the ITT population and the subgroup with visceral disease (sVD) according to a prespecified graphical testing scheme. Kaplan-Meier method and Cox proportional hazards models were used. Reported P values are 2-sided.

Results

OS in the ITT Population

OS in the ITT Population

A total of 493 women were randomized 2:1 to receive abema plus an NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, 7% of patients were still receiving treatment in the abemaciclib arm vs 3% in the placebo arm. In the ITT population, 314 OS events were observed (198 deaths among 328 patients [60%] in the abemaciclib arm and 116 among 165 [70%] in the placebo arm) (HR, 0.804; 95% CI, 0.637-1.015; P = .0664 [not significant (NS)]). Median OS was 66.8 months in the abemaciclib arm and 53.7 months in the placebo arm (a numerical difference of 13.1 months) in the ITT population. Results were consistent in the sVD with abema vs placebo (median OS, 63.7 vs 48.8 months; HR, 0.758; 95% CI, 0.558-1.030; P = .0757 [NS]). Consistent OS differences were observed across prespecified subgroups. PFS benefit was sustained (median PFS, 29.0 vs 14.8 months; HR, 0.535; 95% CI, 0.429-0.668; nominal P <.0001). CFS was also improved with abemaciclib vs placebo (median CFS, 46.7 vs 30.6 months; HR, 0.693; 95% CI, 0.557-0.863; nominal P = .0010). No new safety signals were observed with longer-
term use.

Conclusions

In patients with HR+/HER2– ABC, abema plus NSAI resulted in numerically longer OS compared to an NSAI alone; however, statistical significance was not reached after a median follow-up of 8.1 years. The clinically meaningful improvement in median OS (> 13 months) combined with the sustained significant improvement in median PFS (> 14 months) and substantial extension in median CFS (> 16 months) continue to support the use of abema in combination with an NSAI as first-line therapy
in ABC.

Articles in this issue

31 Adjuvant Abemaciclib Plus Endocrine Therapy for HR+, HER2–, High-Risk Early Breast Cancer: Results From a Preplanned MonarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes
31 Adjuvant Abemaciclib Plus Endocrine Therapy for HR+, HER2–, High-Risk Early Breast Cancer: Results From a Preplanned MonarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes
32 Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy Followed by Adjuvant Pembrolizumab or Placebo for Early-Stage Triple- Negative Breast Cancer: Updated Event-Free Survival Results From the Phase 3 KEYNOTE-522 Study
32 Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy Followed by Adjuvant Pembrolizumab or Placebo for Early-Stage Triple- Negative Breast Cancer: Updated Event-Free Survival Results From the Phase 3 KEYNOTE-522 Study
33 MammaPrint® and BluePrint® Predict Anthracycline Chemosensitivity in Patients With HR+HER2– Early-Stage Breast Cancer Enrolled in FLEX
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34 How Mobile Computing Devices Offer Support for Classic and Molecular Multidisciplinary and Tumor Boards
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36 MONARCH 3: Final Overall Survival Results of Abemaciclib Plus a Nonsteroidal Aromatase Inhibitor as First-Line Therapy for HR+/HER2– Advanced Breast Cancer
36 MONARCH 3: Final Overall Survival Results of Abemaciclib Plus a Nonsteroidal Aromatase Inhibitor as First-Line Therapy for HR+/HER2– Advanced Breast Cancer
37 Estimating the Direct and Indirect Resource Burden of Treatment Management With Current Standard of Care or Elacestrant for ER+, HER2–, ESR1-Mutated Advanced or Metastatic Breast Cancer Patients: A Population- Level Provider Model
37 Estimating the Direct and Indirect Resource Burden of Treatment Management With Current Standard of Care or Elacestrant for ER+, HER2–, ESR1-Mutated Advanced or Metastatic Breast Cancer Patients: A Population- Level Provider Model
38 Influence of Race on Attainment of Textbook Oncologic Outcome Following Modified Radical Mastectomy for Breast Cancer
38 Influence of Race on Attainment of Textbook Oncologic Outcome Following Modified Radical Mastectomy for Breast Cancer
39 The Influence of Reconstruction Type on Outcomes in Women Undergoing Mastectomy With Immediate Reconstruction:  A Nationwide Study
39 The Influence of Reconstruction Type on Outcomes in Women Undergoing Mastectomy With Immediate Reconstruction: A Nationwide Study
40 Ethnic Disparities in Complication Rates and Outcomes  of Nipple-Sparing Mastectomy:  A Comprehensive Analysis
40 Ethnic Disparities in Complication Rates and Outcomes of Nipple-Sparing Mastectomy: A Comprehensive Analysis
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42 Transitional Lymphedema: Understanding the Temporal Dynamics Post-Axillary Surgery
42 Transitional Lymphedema: Understanding the Temporal Dynamics Post-Axillary Surgery
43 Impact of Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) on Postoperative Complication Rates in Mastectomy With Immediate Prosthetic-Based Breast Reconstruction
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44 Variant of Uncertain Significance (VUS) Genetic Testing Results and Mastectomy Choice in Lumpectomy-Eligible Patients
45 Application of the 7-Gene Biosignature in Palpable Versus Nonpalpable Ductal Carcinoma In Situ in a Black Patient Population: Does Palpability Suggest a More Aggressive Genomic Risk?
45 Application of the 7-Gene Biosignature in Palpable Versus Nonpalpable Ductal Carcinoma In Situ in a Black Patient Population: Does Palpability Suggest a More Aggressive Genomic Risk?
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