Overall Survival with Palbociclib and Fulvestrant in Women with HRþ/HER2¯ ABC: Updated Exploratory Analyses of PALOMA-3, a Double-blind, Phase III Randomized Study

Massimo Cristofanilli, Hope S. Rugo, Seock Ah Im, Dennis J. Slamon, Nadia Harbeck, Igor Bondarenko, Norikazu Masuda, Marco Colleoni, Angela DeMichele, Sherene Loi, Hiroji Iwata, Ben O’Leary, Fabrice André, Sibylle Loibl, Eustratios Bananis, Yuan Liu, Xin Huang, Sindy Kim, Maria Jose Lechuga Frean, Nicholas C. Turner

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    91 Citations (Scopus)

    Résumé

    Purpose: To conduct an updated exploratory analysis of overall survival (OS) with a longer median follow-up of 73.3 months and evaluate the prognostic value of molecular analysis by circulating tumor DNA (ctDNA). Patients and Methods: Patients with hormone receptor–positive/ human epidermal growth factor receptor 2–negative (HRþ/HER2¯) advanced breast cancer (ABC) were randomized 2:1 to receive palbociclib (125 mg orally/day; 3/1 week schedule) and fulvestrant (500 mg intramuscularly) or placebo and fulvestrant. This OS analysis was performed when 75% of enrolled patients died (393 events in 521 randomized patients). ctDNA analysis was performed among patients who provided consent. Results: At the data cutoff (August 17, 2020), 258 and 135 deaths occurred in the palbociclib and placebo groups, respectively. The median OS [95% confidence interval (CI)] was 34.8 months (28.8–39.9) in the palbociclib group and 28.0 months (23.5–33.8) in the placebo group (stratified hazard ratio, 0.81; 95% CI, 0.65–0.99). The 6-year OS rate (95% CI) was 19.1% (14.9–23.7) and 12.9% (8.0–19.1) in the palbociclib and placebo groups, respectively. Favorable OS with palbociclib plus fulvestrant compared with placebo plus fulvestrant was observed in most subgroups, particularly in patients with endocrine-sensitive disease, no prior chemotherapy for ABC and low circulating tumor fraction and regardless of ESR1, PIK3CA, or TP53 mutation status. No new safety signals were identified. Conclusions: The clinically meaningful improvement in OS associated with palbociclib plus fulvestrant was maintained with >6 years of follow-up in patients with HRþ/HER2¯ABC, supporting palbociclib plus fulvestrant as a standard of care in these patients.

    langue originaleAnglais
    Pages (de - à)3433-3442
    Nombre de pages10
    journalClinical Cancer Research
    Volume28
    Numéro de publication16
    Les DOIs
    étatPublié - 15 août 2022

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