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William J. Gradishar, MD, FACP, FASCO


ASCO 2023: SONIA Trial Analysis Offers Insight on Timing of CDK4/6 Inhibitor Therapy

By: Celeste L. Dixon
Posted: Thursday, June 15, 2023

The use of CDK4/6 inhibitors, when added to first-line versus second-line endocrine therapy, does not provide a clinically meaningful progression-free survival benefit in women with hormone receptor–positive, HER2-negative advanced breast cancer, new study results revealed. What’s more, first-line use extends the time on CDK4/6 inhibitors by a median of 16.4 months, increasing toxicity and costs. These results, part of the primary outcome analysis of the randomized phase III SONIA trial, were presented by Gabe S. Sonke, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and colleagues at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract LBA1000).

Although most international guidelines currently advise first-line use of CDK4/6 inhibitors, the team said that based on their findings, second-line use may…be a preferred option for the majority of patients.”

The trial included 1,050 pre- and postmenopausal women with measurable or evaluable disease who received no prior therapy for hormone receptor–positive, HER2-negative advanced breast cancer and who were being treated in 74 Dutch hospitals. The investigators said that (neo)adjuvant therapy was allowed if the disease-free interval after nonsteroidal aromatase inhibitor treatment was more than 12 months.

With the patients randomly assigned (1:1) and after a median follow-up of 37.7 months, the median difference of time from randomization to second objective disease progression was not significant (P = .14): It was 31.0 months on first-line treatment with a nonsteroidal aromatase inhibitor plus a CDK4/6 inhibitor, followed upon disease progression by fulvestrant versus 27.8 months on first-line treatment with a nonsteroidal aromatase inhibitor, followed upon disease progression by fulvestrant plus a CDK4/6 inhibitor.

Choice among the available CDK4/6 inhibitors—abemaciclib, palbociclib, or ribociclib—was a stratification factor and was left to the discretion of the treating physician. The treatment effect ultimately was consistent across the levels of predefined subgroups. The median time on CDK4/6 inhibitors was 24.7 months with first-line use of CDK4/6 inhibition and 8.3 months second-line use, for a difference of 16.4 months.

Disclosure: The study authors’ disclosure information can be found at

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