Real-world effectiveness of palbociclib in combination with an aromatase inhibitor in HR+/HER2- bone-only metastatic breast cancer

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) are more effective than ET alone in diverse populations of patients with HR+/HER2− metastatic breast cancer (MBC). However, real-world effectiveness data for CDK4/6 inhibitors plus ET combination in bone-only MBC are limited. Methods: This retrospective, real-world study compared clinical outcomes of first-line (1L) palbociclib (PAL) plus an aromatase inhibitor (AI) with AI alone in bone-only MBC using data from the US-based, nationwide Flatiron Health Research database. Eligible patients had HR+/HER2− bone-only MBC, were ≥18 years of age, and started 1L PAL + AI or AI alone from February 2015 to June 2022. Stabilized inverse probability of treatment weighting (sIPTW) was used to balance baseline characteristics. Overall survival (OS), real-world progression-free survival (rwPFS), and time to chemotherapy (TTC) were evaluated. Results: Of 974 eligible patients with bone-only MBC, 538 received PAL + AI and 436 received AI alone. After sIPTW, baseline patient characteristics were balanced between treatment groups. Median follow-up was 31.9 months for the PAL + AI group and 35.8 months for the AI group. After sIPTW, the PAL + AI group compared with the AI group had a significantly longer OS (median 63.4 vs 51.3 months; HR = 0.78; 95% CI, 0.64–0.97, P = 0.0221), rwPFS (median 23.0 vs 18.2 months; HR = 0.72; 95% CI, 0.59–0.87, P = 0.0008), and TTC (median 47.9 vs 40.6 months; HR = 0.79; 95% CI, 0.66–0.96, P = 0.016). Consistent results were observed in unadjusted and sensitivity analyses. Conclusion: This real-world study demonstrates that first-line PAL + AI versus AI alone was associated with prolonged OS, rwPFS, and TTC in patients with HR+/HER2− bone-only MBC. Trial registration number: NCT06495164.