Abstract 227P
Background
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.
Methods
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).
Results
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).
Conclusions
Prevalence of survival outcomes encourages the rationale of using CDKi in 2L treatment among the majority of pts including subgroups with poor prognostic factors.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.