Final Survival Results from the Penelope-B trial investigating palbociclib vs placebo for patients with high-risk HR+/HER2- breast cancer and residual disease after neoadjuvant chemotherapy – PENELOPE-B
Mené sur 1 250 patientes atteintes d'un cancer du sein HR+ HER2- présentant une maladie résiduelle à haut risque de récidive après une chimiothérapie néoadjuvante (durée médiane de suivi : 77,8 mois), cet essai évalue l'efficacité, du point de vue de la survie sans maladie invasive, de l'ajout de palbociclib à un traitement endocrinien pendant un an
Background: The addition of 1-year of palbociclib to endocrine therapy (ET) did not improve invasive disease-free survival (iDFS) compared to placebo in the PENELOPE-B trial. Here we report the final survival results for the PENELOPE-B trial.
Methods: The PENELOPE-B trial investigated whether adding 1 year of palbociclib to ET in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) patients with residual disease and high relapse risk (CPS-EG score ≥3 or 2 and ypN+) after taxane-based neoadjuvant chemotherapy would improve patient survival. Patients (n=1250) were randomly assigned to receive either palbociclib 125 mg or placebo d1-21 q4w for 13 cycles in addition to ET.
Results: After a median follow-up of 77.8 months, we recorded 225 deaths (108 palbociclib; 117 placebo) with 6-year overall survival (OS) rate of 82.4% in the palbociclib arm vs. 80.3% in the placebo arm [hazard rationHR0.87, 95% CI 0.67-1.14, p=0.31]. No significant improvement was noted for palbociclib vs placebo for iDFS, distant disease-free survival (DDFS) or locoregional relapse rate (LRR), even with longer follow-up. Upon stratified analysis, we found no benefits across major subgroups. However, exploratory post-hoc analyses of the lobular BC (LBC) subgroup indicated a trend towards better survival outcomes in favour of palbociclib HR of 0.45 (95% CI 0.19-1.07, p=0.062) for OS and 0.52 (95% CI 0.28-0.97, p=0.035) for iDFS.
Conclusion: The study concluded that palbociclib did not significantly improve survival outcomes in the overall population. Exploratory post-hoc analyses suggested a trend towards better iDFS outcome in patients with lobular breast cancer receiving palbociclib.