To Örebro University

BACKGROUND: Nationwide studies on the prevalence, characteristics and long-term prognosis of patients with early breast cancer and a potential indication for adjuvant CDK4/6 inhibitors are lacking.

METHODS: We leveraged a prospectively collected nationwide cohort of all patients treated for breast cancer in Sweden in 2007-2023 and identified patients fulfilling the monarchE and/or the NATALEE eligibility criteria, to estimate the proportion of eligible patients for adjuvant CDK4/6 inhibitors and their outcomes. Overall survival (OS) was the primary endpoint of interest. In addition, we compared distant relapse-free survival and OS of a patient subset treated in the Stockholm-Gotland region in 2012-2020 to patients enrolled in the phase 3 PANTHER trial (NCT00798070) in 2007-2011, before and after alignment of key inclusion criteria.

FINDINGS: Of 52,602 patients with ER-positive, HER2-negative breast cancer, 9553 (18.2%) fulfilled both the monarchE and the NATALEE criteria, 9800 (18.6%) fulfilled the NATALEE criteria only and 745 patients (1.4%) fulfilled the monarchE criteria only. Median follow-up was 6.87 years. Ten-year OS rates were 65.7% (95% CI 65.3%-67.0%) for monarchE-eligible and 70.2% (95% CI 69.3%-71.1%) for NATALEE-eligible patients, and 84.0% (95% CI 83.4%-84.6%) for non-eligible, 75.5% (74.4$-76.7%) for NATALEE-only eligible and 64.3% (95% CI 62.9%-65.7%) for concordant eligible patients for both studies (p < 0.0001). Before alignment of inclusion criteria, patients treated within the PANTHER trial had improved outcomes compared to those treated in clinical routine. However, the differences in outcomes disappeared after alignment.

INTERPRETATION: These results inform on the prevalence and prognosis of candidates for adjuvant CDK4/6 inhibitors at a nationwide level. FUNDING: Cancerfonden, Bröstcancerförbundet, Radiumhemmets Forskningsfonder, Amgen, Roche, Sanofi-Aventis.