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, M; Rugo, HS; Im, SA; Slamon, DJ; Harbeck, N; Bondarenko, I; Masuda, N; Colleoni, M; DeMichele, A; Loi, S; Iwata, H; O&#39;Leary, B; Andre, F; Loibl, S; Bananis, E; Liu, Y; Huang, X; Kim, S; Lechuga Frean, MJ; Turner, NC

Author(s): Cristofanilli, M; Rugo, HS; Im, SA; Slamon, DJ; Harbeck, N; Bondarenko, I; Masuda, N; Colleoni, M; DeMichele, A; Loi, S; Iwata, H; O'Leary, B; Andre, F; Loibl, S; Bananis, E; Liu, Y; Huang, X; Kim, S; Lechuga Frean, MJ; Turner, NC;
Details: Publication Year 2022-08-15,Volume 28,Issue #16,Page 3433-3442
Journal Title: Clinical Cancer Research
Publication Type: Research article
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, supporting palbociclib plus fulvestrant as a standard of care in these patients.
Keywords: Antineoplastic Combined Chemotherapy Protocols/adverse effects; *Breast Neoplasms/drug therapy/genetics/metabolism; Double-Blind Method; Female; Fulvestrant; Humans; Piperazines; Pyridines; *Receptor, ErbB-2/metabolism
Department(s): Medical Oncology; Laboratory Research
PubMed ID: 35552673
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-22-0305
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-22-0305
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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Last Modified: 2024-10-18 05:07:17