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

Cristofanilli, Massimo; Rugo, Hope S.; Im, Seock-Ah; Slamon, Dennis J.; Harbeck, Nadia; Bondarenko, Igor; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Iwata, Hiroji; O'Leary, Ben; Andre, Fabrice; Loibl, Sibylle; Bananis, Eustratios; Liu, Yuan; Huang, Xin; Kim, Sindy; Frean, Maria Jose Lechuga und Turner, Nicholas C. (2022): Overall Survival with Palbociclib and Fulvestrant in Women with HR+/HER2(- )ABC: Updated Exploratory Analyses of PALOMA-3, a Double-blind, Phase III Randomized Study. In: Clinical Cancer Research, Bd. 28, Nr. 16: S. 3433-3442

Abstract

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 (HR+/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 HR+/HER2(-) ABC, support-ing palbociclib plus fulvestrant as a standard of care in these patients.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1078-0432
• Sprache: Englisch