PMID- 38011835
OWN - NLM
STAT- Publisher
LR  - 20231127
IS  - 1423-0232 (Electronic)
IS  - 0030-2414 (Linking)
DP  - 2023 Nov 27
TI  - A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for 
      Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution 
      Experience.
PG  - 1-11
LID - 10.1159/000534953 [doi]
AB  - INTRODUCTION: Alpelisib is approved in combination with endocrine therapy (ET) to 
      treat patients with hormone receptor-positive (HR+), human epidermal growth 
      factor receptor 2-negative (HER2-) progressive metastatic breast cancer (MBC). 
      The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, 
      while alpelisib improves outcomes compared to placebo, it is also associated with 
      clinically relevant adverse events (AEs). There is a pressing need for improved 
      knowledge on the effectiveness and tolerability of this agent in real-world 
      patient populations. METHODS: We conducted a retrospective cohort study of 
      patients with HR+, HER2- MBC treated with alpelisib and ET. We assessed the 
      safety, tolerability, and effectiveness of alpelisib in a real-world population. 
      Deidentified patient-, tumor-, and outcome-related data, including AEs, were 
      collected and summarized. Kaplan-Meier methods were applied for survival 
      analyses, and stratified analyses of interest were conducted. A p value <0.05 
      was considered statistically significant. RESULTS: A total of 76 women treated 
      with alpelisib + ET were included in our cohort. Most had been previously treated 
      with cyclin-dependent kinase (CDK) 4/6 inhibitors and chemotherapy for MBC. The 
      estimated median progression-free survival was 5.2 months (95% CI, 4.1-8.0). The 
      median overall survival was longer among patients without prior everolimus 
      therapy (hazard ratio, 4.28 [95% CI, 1.64-11.16]; p = 0.0012), and no significant 
      outcome differences were observed between patients treated with different 
      starting doses of alpelisib. Approximately 31.6% of patients permanently 
      discontinued alpelisib due to AEs, and 32.9% had at least one dose reduction. The 
      most common grade 3/4 AEs were hyperglycemia (21%), fatigue (13.2%), and diarrhea 
      (10.5%). CONCLUSIONS: For progressive HR+, HER2- MBC, alpelisib + ET showed 
      effectiveness in a real-world patient population that was comparable to published 
      clinical trial data, regardless of starting dose. However, the effectiveness of 
      alpelisib following previous everolimus exposure may be limited and, hence, 
      should be a consideration to decide sequencing of therapy in these patients. 
      Patients treated with alpelisib are at risk for clinically relevant AEs and 
      require close monitoring.
CI  - (c) 2023 S. Karger AG, Basel.
FAU - Sarfraz, Humaira
AU  - Sarfraz H
AD  - Department of Hematology/Oncology, H. Lee Moffitt Cancer Center and Research 
      Institute, Tampa, Florida, USA.
FAU - Bari, Shahla
AU  - Bari S
AD  - Department of Hematology/Oncology, Duke University, Durham, North Carolina, USA.
FAU - Whiting, Junmin
AU  - Whiting J
AD  - Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and 
      Research Institute, Tampa, Florida, USA.
FAU - Sur, Melissa
AU  - Sur M
AD  - Clinical Science, University of South Florida, Tampa, Florida, USA.
FAU - Mo, Qianxing
AU  - Mo Q
AD  - Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and 
      Research Institute, Tampa, Florida, USA.
FAU - Armitage, Melissa
AU  - Armitage M
AD  - Department of Pharmacy, H Lee Moffitt Cancer Center and Research Institute, 
      Tampa, Florida, USA.
FAU - Costa, Ricardo L B
AU  - Costa RLB
AD  - Department of Breast Oncology, H Lee Moffitt Cancer Center and Research 
      Institute, Tampa, Florida, USA.
LA  - eng
PT  - Journal Article
DEP - 20231127
PL  - Switzerland
TA  - Oncology
JT  - Oncology
JID - 0135054
SB  - IM
OTO - NOTNLM
OT  - Adverse event
OT  - Alpelisib
OT  - Breast cancer
OT  - Outcomes
EDAT- 2023/11/28 00:42
MHDA- 2023/11/28 00:42
CRDT- 2023/11/27 18:25
PHST- 2023/09/28 00:00 [received]
PHST- 2023/10/28 00:00 [accepted]
PHST- 2023/11/28 00:42 [medline]
PHST- 2023/11/28 00:42 [pubmed]
PHST- 2023/11/27 18:25 [entrez]
AID - 000534953 [pii]
AID - 10.1159/000534953 [doi]
PST - aheadofprint
SO  - Oncology. 2023 Nov 27:1-11. doi: 10.1159/000534953.