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A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer

 Yen-Shen Lu  ;  Keun Seok Lee  ;  Tsu-Yi Chao  ;  Ling-Ming Tseng  ;  Imjai Chitapanarux  ;  Shin-Cheh Chen  ;  Chien-Ting Liu  ;  Joohyuk Sohn  ;  Jee Hyun Kim  ;  Yuan-Ching Chang  ;  Youngsen Yang  ;  Kanjana Shotelersuk  ;  Kyung Hae Jung  ;  Roberta Valenti  ;  Cassandra Slader  ;  Melissa Gao  ;  Yeon Hee Park 
 CLINICAL CANCER RESEARCH, Vol.27(2) : 408-417, 2021-01 
Journal Title
Issue Date
Aminopyridines ; Antineoplastic Combined Chemotherapy Protocols / adverse effects ; Breast Neoplasms* / drug therapy ; Cyclin-Dependent Kinase 4 ; Female ; Goserelin* / adverse effects ; Humans ; Morpholines ; Phosphatidylinositol 3-Kinases ; Receptor, ErbB-2 / genetics ; Receptor, ErbB-2 / therapeutic use ; Tamoxifen / therapeutic use ; Thiazoles
Purpose: This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC).

Patients and methods: This study enrolled premenopausal women with HR+, HER2- ABC. Patients received tamoxifen (20 mg once daily) and goserelin acetate (3.6 mg every 28 days) with either alpelisib (350 mg once daily; n = 16) or buparlisib (100 mg once daily; n = 13) in 28-day cycles until MTD was observed.

Results: The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group.

Conclusions: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR+, HER2- ABC.See related commentary by Clark et al., p. 371.

Trial registration: ClinicalTrials.gov NCT02058381.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Joo Hyuk(손주혁) ORCID logo https://orcid.org/0000-0002-2303-2764
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