Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2- metastatic breast cancer in the US real-world setting

H. S. Rugo (1), R. M. Layman (2), F. Lynce (3), X. Liu (4), B. Li (4), L. McRoy (4), A. B. Cohen (5, 6), M. Estevez (5), G. Curigliano (7, 8), A. Brufsky (9)
(1) University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco
(2) The University of Texas MD Anderson Cancer Center, Houston
(3) Dana-Farber Cancer Institute, Boston
(4) Pfizer Inc., New York
(5) Flatiron Health Inc., New York
(6) NYU Langone School of Medicine, New York, USA
(7) European Institute of Oncology, IRCCS, Milan
(8) Department of Oncology and Hemato-Oncology, University of Milano, Milan, Italy
(9) UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, USA

Background: Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclindependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several realworld studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.

Patients and methods: This retrospective study used real-world data from the Flatiron Health electronic health recordderived deidentified longitudinal database. Patients with HR+/HER2- mBC aged ≥18 years at mBC diagnosis started 1L CDK4/6i therapy (index treatment) between February 2015 and November 2023, with a potential ≥6-month follow-up. OS was defined as months from start of index treatment to death. Stabilized inverse probability of treatment weighting (sIPTW; primary analysis) was used to balance baseline patient characteristics. Multivariable Cox proportional hazards model was carried out as a sensitivity analysis.

Results: Of 9146 eligible patients, 6831, 1279, and 1036 received palbociclib plus AI, ribociclib plus AI, or abemaciclib plus AI, respectively. After sIPTW, baseline characteristics were balanced between treatment groups. After sIPTW, no significant OS differences were found between treatment groups [ribociclib versus palbociclib: adjusted hazard ratio (aHR) 0.98, 95% confidence interval (CI) 0.87-1.10, p = 0.7531; abemaciclib versus palbociclib: aHR 0.95, 95% CI 0.84-1.08, p = 0.4292; abemaciclib versus ribociclib: aHR 0.97, 95% CI 0.82-1.14, p = 0.6956]. Sensitivity analysis including a subanalysis of patients who started index treatment in 2017 or later also showed no significant OS differences between treatment groups.

Conclusions: This large real-world study suggested that there were no significant OS differences between 1L ribociclib, abemaciclib, and palbociclib in combination with an AI for patients with HR+/HER2- mBC. These findings together with other factors such as safety and quality of life are helpful in the selection of CDK4/6i combination therapy for patients with HR+/HER2- mBC.


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