Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real-world population of hormone receptor-positive (ER+/PgR+), HER2-negative advanced breast cancer (ABC) patients: a multicenter Italian experience

Breast Cancer Res Treat. 2017 Jun;163(3):587-594. doi: 10.1007/s10549-017-4213-9. Epub 2017 Mar 28.

Abstract

Aim: This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability.

Methods: 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C).

Results: RR was 29.8% (A), 27.8% (B) (p = 0.953), and not evaluable (C). PFS was 9 months (95% CI 7-11) (A), 10 months (95% CI 9-11) (B), and 5 months (95% CI 2-8) (C), p = 0.956. OS was 38 months (95% CI 24-38) (A), median not reached (B), and 13 months (95% CI 10-25) (C), p = 0.002. Adverse events were stomatitis 57.7% (11.0% grade 3-4), asthenia 46.0% (6.1% grade 3-4), hypercholesterolemia 46.0% (0.6% grade 3-4), and hyperglycemia 35.6% (5.5% grade 3-4). The main reason for discontinuation/interruption was grade 2-3 stomatitis.

Conclusions: No correlation was found between dose intensity (5 vs. 10 mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy.

Keywords: Breast cancer; Dose intensity; Everolimus; Real-world population; Side effects.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androstadienes / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Drug-Related Side Effects and Adverse Reactions / classification
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Everolimus / administration & dosage*
  • Female
  • Humans
  • Italy / epidemiology
  • Middle Aged
  • Neoplasm Staging
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / genetics
  • Stomatitis / chemically induced
  • Stomatitis / genetics
  • Stomatitis / pathology

Substances

  • Androstadienes
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Everolimus
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • exemestane