Effectiveness outcomes by treatment-free interval among patients receiving palbociclib plus endocrine therapy in HR+/HER2− advanced breast cancer in the real-world setting: Results from the PERFORM study.

Abstract

1061 Background: Combination of CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) is first-line (1L) standard of care for patients (pts) with HR+/HER2- advanced breast cancer (ABC). Treatment-free interval (TFI) is an established prognostic factor in ABC. Shorter TFI is associated with more aggressive disease biology, inferior treatment outcomes, and reduced overall survival (OS). Real-world (RW) evidence complements clinical trials by providing insights into pts underrepresented in clinical trials. We present interim analysis 5 (IA5) of the PERFORM study, evaluating outcomes by TFI in pts receiving 1L palbociclib + ET. Methods: The prospective, non-interventional study PERFORM (NCT04767594) enrolled pts across Germany and Austria receiving 1L palbociclib + ET. Primary endpoint is progression-free survival (PFS). Secondary endpoints include second line (2L) PFS, PFS2 (time from 1L start to progression on 2L or death) and OS. Tumor assessments followed local medical standards. Quality of life (QoL) was assessed using FACT-B questionnaires. Pts were stratified by TFI, defined as time from last (neo)adjuvant treatment to recurrence: >12 months, ≤12 months, and de novo advanced disease. Time-to-event endpoints were estimated using the Kaplan-Meier method. Results: At database cutoff (Sep 30th, 2025), 1268 pts were included in IA5 and 1010 pts had available TFI data for subgroup analysis (TFI >12 months: 373 pts; ≤12 months: 133 pts; de novo: 504 pts). Median age was 69.5, 64.4, and 68.8 years, respectively. Pts with TFI ≤12 months showed a more aggressive disease profile such as higher rates of G3 tumors, N2-3 nodal status and liver metastasis compared to other TFI subgroups. Overall median PFS was 25.5 months (95% CI: 23.0-28.6), while median PFS was 29.2 months (95% CI: 23.3-33.1) for TFI >12 months, 14.6 months (95% CI: 9.3-19.4) for TFI ≤12 months, and 31.5 months (95% CI: 26.5-36.7) for pts with de novo disease. Median PFS2 was 39.0 (95% CI:33.7-51.4), 21.2 (95% CI: 17.4-37.0), and 40.9 months (95% CI: 37.0-46.9) for TFI >12, ≤12, and de novo, respectively. Median OS was not reached for TFI>12 months and was 37.4 and 52.8 months for TFI ≤12 and de novo, respectively. QOL with 1L therapy was maintained in all subgroups. Conclusions: The PERFORM IA5 supports TFI as a relevant prognostic factor for pts treated with palbociclib + ET in the 1L RW setting. QOL was maintained in TFI subgroups. Longest clinical benefit was observed in pts with TFI > 12 months and those with de novo disease. Treatment was associated with shorter clinical outcome in pts with TFI≤12 months compared to those in other TFI subgroups. These results complement those in the RCT setting.