SONIA Trial Finds No Overall Survival Benefit for First-Line CDK4/6 Inhibitors in Advanced Breast Cancer
The SONIA trial found no overall survival benefit for first-line CDK4/6 inhibitors versus second-line use in advanced HR+/HER2- breast cancer. Median survival was 47.9 vs 48.1 months, though post hoc analysis suggested benefit in premenopausal patients. First-line treatment was associated with more severe adverse events.
First-line use of cyclin-dependent kinase 4 and 6 inhibitors did not improve overall survival compared with second-line use in hormone receptor-positive, ERBB2-negative advanced breast cancer, according to results from the phase III randomized SONIA trial. Median overall survival was 47.9 months with first-line CDK4/6 inhibitor treatment versus 48.1 months with second-line use, showing no significant difference. A post hoc subgroup analysis suggested potential overall survival benefit with first-line use in premenopausal patients but not in postmenopausal patients.
The SONIA trial enrolled 1050 patients with hormone receptor-positive, ERBB2-negative advanced breast cancer who had not received prior treatment for advanced disease, with a median age of 64 years. Participants were randomly assigned 1:1 to receive either aromatase inhibitor plus CDK4/6 inhibitor as first-line treatment followed by fulvestrant or aromatase inhibitor followed by fulvestrant plus CDK4/6 inhibitor as second-line treatment.
The analysis included a median follow-up of 58.5 months, with data cutoff on September 1, 2024. The hazard ratio for overall survival was 0.91, indicating no significant difference between treatment sequences. Post hoc subgroup analysis revealed an overall survival benefit with first-line use in premenopausal patients but not in postmenopausal patients, with a significant interaction for menopausal status.
First-line versus second-line CDK4/6 inhibitor use was associated with more grade 3 or higher adverse events, with 3400 events in the first-line group compared to 2242 events in the second-line group. Among patients who discontinued second-line treatment, subsequent anticancer therapy patterns were similar between groups.
The research was conducted across 74 Dutch hospitals in compliance with the Declaration of Helsinki and International Guidelines for Good Clinical Practice. A potential limitation was the predominant use of palbociclib in the study, reflecting national reimbursement timelines of individual agents. Additionally, the evolving treatment landscape since the study's start, with several new agents becoming available after progression on CDK4/6 inhibitor treatment, may affect the generalizability of findings.