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Clarifying the role of SONIA: supporting academic evidence on CDK4/6 inhibitor timing

Nature Reviews Clinical Oncology volume 22, page 701 (2025)Cite this article

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We have read with interest the News & Views article by Shani Paluch-Shimon and Fatima Cardoso (Paluch-Shimon, S., Cardoso, F. The SONIA trial shows the power and challenges of academic research. Nat. Rev. Clin. Oncol. 22, 311–312 (2025))1, which offers a perspective on the landmark SONIA trial2. We respectfully disagree with some of their conclusions.

Previous trials have confirmed the role of CDK4/6 inhibitors in the treatment of patients with advanced-stage HR+HER2− breast cancer3,4,5. However, trials testing these agents in the first-line setting often did not ensure that patients in the control arm received CDK4/6 inhibitors on disease progression. As a result, only ~30–35% of patients in those trials received such treatment, biasing results in favour of early use and potentially overestimating benefit4,5. SONIA directly compared two treatment sequences in a real-world setting with protocol-defined crossover, pragmatically reflecting clinical decision-making on optimal timing of treatment2.

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Authors and Affiliations

  1. Department of Internal Medicine, Maimonides Medical Center, Brooklyn, NY, USA

    Avi Petroff

  2. Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Avi Petroff & Daniel A. Goldstein

  3. Division of Medical Oncology, Princess Margaret Hospital Cancer Center, Toronto, Ontario, Canada

    Ian F. Tannock

  4. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Ian F. Tannock

  5. Center for Cancer Economics, Davidoff Center, Rabin Medical Center, Petach Tikva, Israel

    Daniel A. Goldstein

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  1. Avi Petroff
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  2. Ian F. Tannock
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Correspondence to Daniel A. Goldstein.

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The authors declare no competing interests.

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Petroff, A., Tannock, I.F. & Goldstein, D.A. Clarifying the role of SONIA: supporting academic evidence on CDK4/6 inhibitor timing. Nat Rev Clin Oncol 22, 701 (2025). https://doi.org/10.1038/s41571-025-01063-5

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