Therapeutic Advances in Medical Oncology (Dec 2023)

Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors

  • Emma Zattarin,
  • Luigi Mariani,
  • Alice Menichetti,
  • Rita Leporati,
  • Leonardo Provenzano,
  • Francesca Ligorio,
  • Giovanni Fucà,
  • Riccardo Lobefaro,
  • Luca Lalli,
  • Andrea Vingiani,
  • Federico Nichetti,
  • Gaia Griguolo,
  • Marianna Sirico,
  • Ottavia Bernocchi,
  • Antonio Marra,
  • Chiara Corti,
  • Paola Zagami,
  • Elisa Agostinetto,
  • Flavia Jacobs,
  • Pierluigi Di Mauro,
  • Daniele Presti,
  • Caterina Sposetti,
  • Carlo Alberto Giorgi,
  • Valentina Guarneri,
  • Rebecca Pedersini,
  • Agnese Losurdo,
  • Daniele Generali,
  • Giuseppe Curigliano,
  • Giancarlo Pruneri,
  • Filippo de Braud,
  • Maria Vittoria Dieci,
  • Claudio Vernieri

DOI
https://doi.org/10.1177/17588359231204857
Journal volume & issue
Vol. 15

Abstract

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Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2− aBC). Objectives: While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown. Design: A multicenter, retrospective-prospective Italian study. Methods: We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2− aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables. Results: We evaluated 638 HR+/HER2− aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66–0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73–0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively). Conclusion: Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2− aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2− aBC treated with ETs plus CDK4/6i.