Comparative efficacy between real-world and randomized studies of palbociclib+endocrine therapy in HR-positive/HER2-negative MBC: systematic-review and meta-analysis
A partir d'une revue systématique de la littérature (12 études), cette méta-analyse évalue, en fonction de la nature des données (données de vie réelle ou données d'essais randomisés), la concordance des résultats thérapeutiques (survie sans progression et survie globale) chez des patientes atteintes d'un cancer du sein HR+ HER2- de stade métastatique et recevant un traitement endocrinien en combinaison avec le palbociclib
Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard-of-care for hormone receptor-positive (HR+)/HER2-negative (HER2−) metastatic breast cancer (MBC). Palbociclib, the first approved CDK4/6i, significantly improved progression-free survival (PFS) in randomized controlled trials (RCTs). However, real-world (RW) outcomes may differ due to broader patient populations. This meta-analysis evaluates the applicability of pivotal RCT findings to RW settings.
Methods: We conducted a systematic review and meta-analysis of RW studies on HR+/HER2− MBC treated with palbociclib+aromatase inhibitors (AI) or fulvestrant, reporting median PFS (mPFS) and/or overall survival (mOS). Pooled mPFS/OS was estimated using the median of medians (MM) and weighted MM (WM). RW estimates were deemed comparable to RCTs if MMPFS/OS or WMPFS/OS fell within RCTs’ 95% confidence intervals (CI). Similar criteria applied to pooled hazard ratios (HR) of PFS/OS for palbociclib+AI vs AI in visceral/non-visceral subgroups.
Results: Twelve RW studies were analyzed. First-line palbociclib+AI MMPFS (22.5 months, 95%CI: 19.5–31.8) aligned with PALOMA-1/2 pooled mPFS (23.9, 95% CI: 20.2–27.6). First-line palbociclib+fulvestrant MMPFS (13.5, 95%CI: 11.6–28.5) exceeded PALOMA-3 (11.2, 95%CI: 9.5–12.9). Second-line palbociclib+fulvestrant MMPFS (11.5 months, 95%CI: 6.3–15.3) was consistent with PALOMA-3. RW first-line mOS (51.2 months, 95%CI: 49.1–53.3) surpassed PALOMA-1/2 pooled mOS (45.7, 95%CI: 37.5–53.8). WMOS (49.1 months, 95%CI: 49.1–53.3) was slightly lower than RCTs (53.7, 95%CI: 37.5–53.8). Palbociclib+AI outperformed AI in RW visceral disease, aligning with RCTs, and showed heterogeneous but favorable benefit in non-visceral disease.
Conclusions: RW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.
JNCI Cancer Spectrum , résumé, 2025