Real-world progression-free survival 2 (PFS2) and tumor response of CDK4/6 inhibitors plus an aromatase inhibitor in patients with HR+/HER2- metastatic breast cancer in US routine clinical practice

Background: Comparative cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) effectiveness data to date are limited to real-world progression-free survival (PFS) and overall survival. Additional effectiveness measures such as time from initial treatment to progression on first subsequent therapy (rwPFS2) and real-world tumor response (rwTR) provide full understanding of CDK4/6i real-world effectiveness. This analysis compared rwPFS2 and rwTR in patients with HR+/HER2− mBC receiving first-line (1L) CDK4/6i plus an aromatase inhibitor (AI) in US routine clinical practice. Patients and methods: P-VERIFY was a retrospective Flatiron Health Research Database analysis of adult patients with HR+/HER2− mBC who started 1L CDK4/6i (palbociclib; ribociclib; abemaciclib) plus AI between February 2015 and November 2023 (N = 9146). rwPFS2 analysis included all 9146 patients while rwTR analysis included 8010 (87.6%) patients who had ≥1 tumor response assessment. Stabilized inverse probability of treatment weighting (sIPTW) was used to balance patient baseline characteristics. A multivariable Cox proportional hazards model was used for sensitivity analysis. Results: After sIPTW, no significant differences were observed across all pairwise treatment comparisons between the CDK4/6i for rwPFS2 and rwTR (all p > 0.05). Findings were generally consistent across subgroups and sensitivity analyses. Findings were also consistent in a separate analysis of patients treated from 2017 onward, corresponding with commercial availability of all three CDK4/6i in the US. Conclusions: This real-world study demonstrated no statistically significant differences in rwPFS2 and rwTR in patients with HR+/HER2− mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an AI, in routine clinical practice in the US. Clinicaltrials gov identifier: NCT06495164.