Endocrine Therapy Plus CDK4/6 in First or Second Line for Hormone (SONIA) Receptor Positive Advanced Breast Cancer

Summary

Given the uncertain benefit in efficacy of adding CDK 4/6 to first rather than second line endocrine treatment, the aim of this project is to evaluate whether the sequence of an aromatase inhibitor plus CDK 4/6 in first line followed by fulvestrant in second line is superior to the sequence of an aromatase inhibitor in first line followed by fulvestrant plus CDK4/6 in second line.

Timeline

Start

2017-11-09

Primary completion

2023-03-06

Completion

2028-12

Publications

• Wortelboer N, van Ommen-Nijhof A, Konings IR, van der Noort V, van den Pol E, Guerrero Paez C, Bakker SD, Hovenga S, Imholz ALT, Kamm YJL, van Leeuwen L, Luykx-de Bakker SA, Mandigers CMPW, van Riel JMGH, Tol J, van de Wouw AJ, Wilting SM, van Leeuwen-Stok AE, Jager A, Sonke GS. Overall Survival With First-Line vs Second-Line CDK4/6 Inhibitor Use in Advanced Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2026 Apr 1;12(4):375-383. doi: 10.1001/jamaoncol.2025.6585.
• Wortelboer N, Kent S, Blommestein HM, van Ommen-Nijhof A, van der Noort V, van den Pol E, Paez CG, Beeker A, Beelen K, Hamming LC, Heijns JB, Honkoop AH, de Jong PC, van Rossum-Schornagel QC, van Schaik-van de Mheen C, Tol J, Tromp-van Driel CS, Vrijaldenhoven S, van Leeuwen-Stok AE, Sonke GS, Jager A, Konings IR. Health-related quality of life with first- vs second-line CDK4/6 inhibitor use in advanced breast cancer: results from the SONIA trial. J Natl Cancer Inst. 2026 Mar 1;118(3):502-510. doi: 10.1093/jnci/djaf334.
• Wortelboer N, Kent S, Konings IR, van Ommen-Nijhof A, van der Noort V, van den Pol E, Guerrero Paez C, van Bekkum ML, van den Berkmortel FWPJ, Droogendijk HJ, Houtsma D, Oosterkamp HM, van der Padt-Pruijsten A, Siemerink EJM, Tol J, van Zweeden AA, van Leeuwen-Stok AE, Sonke GS, Jager A, Blommestein HM. Health economic outcomes and costs of CDK4/6 inhibitor use in first- versus second-line for advanced breast cancer: A cost-effectiveness analysis of the phase 3 SONIA trial. Eur J Cancer. 2025 Dec 9;231:116051. doi: 10.1016/j.ejca.2025.116051. Epub 2025 Oct 25.
• Jongbloed EM, Wortelboer N, de Weerd V, Beaufort CM, Ruigrok-Ritstier K, Van MN, Kraan J, van Zweeden AA, van der Padt-Pruijsten A, Hamming LC, Konings IR, Sonke GS, Oomen-de Hoop E, Martens JWM, Jager A, Wilting SM. Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer: circulating tumor DNA analysis of a randomized phase 3 trial. Nat Med. 2025 Nov;31(11):3662-3667. doi: 10.1038/s41591-025-03935-w. Epub 2025 Sep 4.
• van Ommen-Nijhof A, Konings IR, van Zeijl CJJ, Uyl-de Groot CA, van der Noort V, Jager A, Sonke GS; SONIA study steering committee. Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer - the SONIA study: study protocol for a randomized controlled trial. BMC Cancer. 2018 Nov 20;18(1):1146. doi: 10.1186/s12885-018-4978-1.

Drugs

Indications