A phase ib study of alpelisib (BYL719), a PI3Kα-specific inhibitor, with letrozole in ER+/HER2- metastatic breast cancer Academic Article uri icon

Overview

MeSH Major

  • Colonic Neoplasms
  • Rectal Neoplasms

abstract

  • Alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%-56%), including five objective responses. Of eight patients remaining on treatment ≥12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER(+)/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro CONCLUSIONS: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER(+) breast cancer are ongoing. Clin Cancer Res; 23(1); 26-34. ©2016 AACR.

publication date

  • January 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5085926

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-16-0134

PubMed ID

  • 27126994

Additional Document Info

start page

  • 26

end page

  • 34

volume

  • 23

number

  • 1