227P The role of CDK4/6 inhibitors in sequencing of endocrine treatment in metastatic breast cancer or can we accept the SONIA trial results in real-world practice?

The recent results from SONIA trial have compromised the current standard of first-line (1L) therapy of hormone receptor-positive HER2-negative metastatic breast cancer (mBC). However, more evidence is needed to confirm the opportunity of reserving cyclin dependent kinases 4/6 inhibitors (CDKi) for second-line (2L) treatment. This strategy may help in reducing toxicity and expenditures without loss of survival benefit. We conducted a retrospective study to compare outcomes of patients (pts) who received CDKi as 1L or 2L treatment of mBC in Moscow City Clinical Oncological Hospital No. 1 since 2020 to 2023. The primary endpoint was time to second disease progression (PFS2), defined as time from the start of 1L to progression on 2L therapy; the secondary endpoint was overall survival (OS). A total of 183 pts represented 3 treatment strategies: cohort A (n=80) received 1L endocrine monotherapy (ET) followed on progression by CDKi + ET; cohort B (n=62) -1L CDKi+ET followed by any ET (+ mTOR or PIK3CA inhibitors) and cohort C (n=41) with chemotherapy (CT) after progression on 1L CDKi + ET. Liver metastases (mts) were present in 10% and 21% in cohorts A and B+C, primary endocrine resistance – 12% and 18% in cohorts A and B+C, respectively. The median follow-up was 44 months. Median PFS2 in cohort A was 54 months which was significantly longer than in cohort B – 30 months (HR 0.3, 95% CI 0.19-0.49) and cohort C – 24 months (HR 0.23, 95% CI 0.13-0.38). The 3-year survival rates were 82%, 68% and 38% in cohorts A, B, C, respectively (HR 0.32, 95% CI 0.17-0.61). Liver mts (HR 0.76, 95% CI 0.6-0.9, p=0.027) and primary endocrine resistance (HR 0.8, 95% CI 0.6-1.0, p=0.08) were associated with poor prognosis in multivariate Cox regression model. In subgroup with liver mts mPFS2 were 25 months in cohort A versus 29 months in cohorts B+C (HR 0.35, 95% CI 0.1-1.0, p=0.05), in endocrine resistant subgroup – 22 and 35 months in cohorts A versus B+C, respectively (HR 0.4, 95% CI 0.1-1.0, p=0.07). Prevalence of survival outcomes encourages the rationale of using CDKi in 2L treatment among the majority of pts including subgroups with poor prognostic factors.