Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial

Author(s): Kevin Kalinsky, MD, MS, FASCO¹; Giampaolo Bianchini, MD²; Erika Hamilton, MD³; Stephanie L. Graff, MD⁴; Kyong Hwa Park, MD, PhD⁵; Rinath Jeselsohn, MD⁶; Umut Demirci, MD, PhD⁷; Miguel Martin, MD, PhD⁸; Rachel M. Layman, MD⁹; Sara A. Hurvitz, MD¹⁰; Sarah Sammons, MD⁶; Peter A. Kaufman, MD¹¹; Montserrat Muñoz, MD¹²; Jiun-I Lai, MD, PhD¹³; Holly Knoderer, MD, MBA, MSc¹⁴; Cynthia Sandoval, PhD¹⁴; Aarti R. Chawla, PhD¹⁴; Bastien Nguyen, PhD¹⁴; Yanhong Zhou, PhD¹⁴; Elizabeth Ravenberg, PhD¹⁴; Lacey M. Litchfield, PhD¹⁴; Lillian Smyth, MD¹⁴; Seth A. Wander, MD, PhD¹⁵;

Source: https://doi.org/10.1200/JCO-24-02086

Dr. Anjan Patel's Thoughts

Yet another combination to consider after CDK4/6i + ET in HR+ MBC!

PURPOSE

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard first-line treatment for hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC); however, disease progression occurs in almost all patients and additional treatment options are needed. Herein, we report outcomes of the postMONARCH trial investigating a switch in ET with/without CDK4/6 inhibition with abemaciclib after disease progression on CDK4/6i.

METHODS

This double-blind, randomized phase III study enrolled patients with disease progression on previous CDK4/6i plus aromatase inhibitor as initial therapy for advanced disease or recurrence on/after adjuvant CDK4/6i + ET. Patients were randomly assigned (1:1) to abemaciclib + fulvestrant or placebo + fulvestrant. The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included PFS by blinded independent central review, objective response rate (ORR), and safety.

RESULTS

This study randomly assigned 368 patients (abemaciclib + fulvestrant, n = 182; placebo + fulvestrant, n = 186). At the primary analysis (258 events), the hazard ratio (HR) was 0.73 (95% CI, 0.57 to 0.95; nominal P = .017), with median PFS 6.0 (95% CI, 5.6 to 8.6) versus 5.3 (95% CI, 3.7 to 5.6) months and 6-month PFS rates of 50% and 37% in the abemaciclib + fulvestrant and placebo + fulvestrant arms, respectively. These results were supported by BICR-assessed PFS (HR, 0.55 [95% CI, 0.39 to 0.77]; nominal P < .001). A consistent treatment effect was seen across major clinical and genomic subgroups, including with/without ESR1 or PIK3CA mutations. Among patients with measurable disease, investigator-assessed ORR was improved with abemaciclib + fulvestrant versus placebo + fulvestrant (17% v 7%; nominal P = .015). No new safety signals were observed, with findings consistent with the known safety profile of abemaciclib.

CONCLUSION

Abemaciclib + fulvestrant significantly improved PFS after disease progression on previous CDK4/6i + ET in patients with HR+, HER2– ABC, offering an additional targeted therapy option for these patients.

Author Affiliations

¹Winship Cancer Institute at Emory University, Atlanta, GA; ²IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy; ³Sarah Cannon Research Institute, Nashville, TN; ⁴Brown University Health, Legorreta Cancer Center at Brown University, Providence, RI; ⁵Korea University Anam Hospital, Korea University, Seoul, South Korea; ⁶Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; ⁷Memorial Ankara Hospital, Ankara, Turkey; ⁸Hospital General Universitario Gregorio Maranon, Universidad Complutense, Madrid, Spain; ⁹MD Anderson Cancer Center, University of Texas, Houston, TX; ¹⁰Fred Hutchinson Cancer Center, University of Washington School of Medicine, Seattle, WA; ¹¹University of Vermont Medical Center, Burlington, VT; ¹²Hospital Clinic and Translational Genomics and Targeted Therapeutics, Institut d’Investigacions Biomediques Pi I Sunyer-IDIBAPS, Barcelona, Spain; ¹³Taipei Veterans General Hospital, Taipei, Taiwan; ¹⁴Eli Lilly and Company, Indianapolis, IN; ¹⁵Massachusetts General Hospital, Harvard University, Boston, MA;

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