Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226

Daniel L. Hertz, William E. Barlow, Kelley M. Kidwell, Kathy S. Albain, Ted A. Vandenberg, Shaker R. Dakhil, Nagendra R. Tirumali, Robert B Livingston, Julie Gralow, Daniel F. Hayes, Gabriel N. Hortobagyi, Rita S. Mehta, James M. Rae

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aims: In the SWOG S0226 trial the combination of anastrozole plus fulvestrant (n = 349) was superior to anastrozole alone (n = 345) in hormone receptor (HR)-positive metastatic breast cancer. Here we report a pharmacokinetic subset analysis investigating a possible drug interaction between anastrozole and fulvestrant. Methods: Post-menopausal patients with HR-positive metastatic breast cancer were randomized to anastrozole with or without concurrent fulvestrant. Blood samples were collected at 2, 4, 6 and 8 months, just prior to receiving the next dose of anastrozole and fulvestrant. Drug concentrations were measured via LC/MS-MS. Anastrozole concentration was compared in patients on anastrozole alone vs. patients on concomitant fulvestrant. Comparisons were made at each time point using parametric tests and over time using a linear mixed effects model. Results: A total of 483 anastrozole concentration measurements were included, 224 samples from 64 patients on the anastrozole alone arm and 259 from 73 patients on the combination arm. The mean anastrozole concentration in the combination arm was significantly lower than that in the anastrozole alone arm at each sample collection time (all P <0.01) and in the mixed effects model (an estimated difference of 9.85 ng ml-1 (95% CI 5.69, 14.00 ng ml-1), P <0.001). Conclusion: A significant pharmacokinetic drug interaction was detected, in which the addition of fulvestrant to anastrozole treatment decreased the trough anastrozole concentration. Further research is needed to verify whether this interaction affects treatment efficacy and to determine the pharmacological mechanism by which this interaction occurs.

Original languageEnglish (US)
JournalBritish Journal of Clinical Pharmacology
DOIs
StateAccepted/In press - 2016

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Breast Neoplasms
Pharmaceutical Preparations
Drug Interactions
anastrozole
fulvestrant
Pharmacokinetics
Hormones
Pharmacology
Research

Keywords

  • Anastrozole
  • Breast cancer
  • Drug interaction
  • Fulvestrant
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226. / Hertz, Daniel L.; Barlow, William E.; Kidwell, Kelley M.; Albain, Kathy S.; Vandenberg, Ted A.; Dakhil, Shaker R.; Tirumali, Nagendra R.; Livingston, Robert B; Gralow, Julie; Hayes, Daniel F.; Hortobagyi, Gabriel N.; Mehta, Rita S.; Rae, James M.

In: British Journal of Clinical Pharmacology, 2016.

Research output: Contribution to journalArticle

Hertz, DL, Barlow, WE, Kidwell, KM, Albain, KS, Vandenberg, TA, Dakhil, SR, Tirumali, NR, Livingston, RB, Gralow, J, Hayes, DF, Hortobagyi, GN, Mehta, RS & Rae, JM 2016, 'Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226', British Journal of Clinical Pharmacology. https://doi.org/10.1111/bcp.12904
Hertz, Daniel L. ; Barlow, William E. ; Kidwell, Kelley M. ; Albain, Kathy S. ; Vandenberg, Ted A. ; Dakhil, Shaker R. ; Tirumali, Nagendra R. ; Livingston, Robert B ; Gralow, Julie ; Hayes, Daniel F. ; Hortobagyi, Gabriel N. ; Mehta, Rita S. ; Rae, James M. / Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226. In: British Journal of Clinical Pharmacology. 2016.
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abstract = "Aims: In the SWOG S0226 trial the combination of anastrozole plus fulvestrant (n = 349) was superior to anastrozole alone (n = 345) in hormone receptor (HR)-positive metastatic breast cancer. Here we report a pharmacokinetic subset analysis investigating a possible drug interaction between anastrozole and fulvestrant. Methods: Post-menopausal patients with HR-positive metastatic breast cancer were randomized to anastrozole with or without concurrent fulvestrant. Blood samples were collected at 2, 4, 6 and 8 months, just prior to receiving the next dose of anastrozole and fulvestrant. Drug concentrations were measured via LC/MS-MS. Anastrozole concentration was compared in patients on anastrozole alone vs. patients on concomitant fulvestrant. Comparisons were made at each time point using parametric tests and over time using a linear mixed effects model. Results: A total of 483 anastrozole concentration measurements were included, 224 samples from 64 patients on the anastrozole alone arm and 259 from 73 patients on the combination arm. The mean anastrozole concentration in the combination arm was significantly lower than that in the anastrozole alone arm at each sample collection time (all P <0.01) and in the mixed effects model (an estimated difference of 9.85 ng ml-1 (95{\%} CI 5.69, 14.00 ng ml-1), P <0.001). Conclusion: A significant pharmacokinetic drug interaction was detected, in which the addition of fulvestrant to anastrozole treatment decreased the trough anastrozole concentration. Further research is needed to verify whether this interaction affects treatment efficacy and to determine the pharmacological mechanism by which this interaction occurs.",
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T1 - Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226

AU - Hertz, Daniel L.

AU - Barlow, William E.

AU - Kidwell, Kelley M.

AU - Albain, Kathy S.

AU - Vandenberg, Ted A.

AU - Dakhil, Shaker R.

AU - Tirumali, Nagendra R.

AU - Livingston, Robert B

AU - Gralow, Julie

AU - Hayes, Daniel F.

AU - Hortobagyi, Gabriel N.

AU - Mehta, Rita S.

AU - Rae, James M.

PY - 2016

Y1 - 2016

N2 - Aims: In the SWOG S0226 trial the combination of anastrozole plus fulvestrant (n = 349) was superior to anastrozole alone (n = 345) in hormone receptor (HR)-positive metastatic breast cancer. Here we report a pharmacokinetic subset analysis investigating a possible drug interaction between anastrozole and fulvestrant. Methods: Post-menopausal patients with HR-positive metastatic breast cancer were randomized to anastrozole with or without concurrent fulvestrant. Blood samples were collected at 2, 4, 6 and 8 months, just prior to receiving the next dose of anastrozole and fulvestrant. Drug concentrations were measured via LC/MS-MS. Anastrozole concentration was compared in patients on anastrozole alone vs. patients on concomitant fulvestrant. Comparisons were made at each time point using parametric tests and over time using a linear mixed effects model. Results: A total of 483 anastrozole concentration measurements were included, 224 samples from 64 patients on the anastrozole alone arm and 259 from 73 patients on the combination arm. The mean anastrozole concentration in the combination arm was significantly lower than that in the anastrozole alone arm at each sample collection time (all P <0.01) and in the mixed effects model (an estimated difference of 9.85 ng ml-1 (95% CI 5.69, 14.00 ng ml-1), P <0.001). Conclusion: A significant pharmacokinetic drug interaction was detected, in which the addition of fulvestrant to anastrozole treatment decreased the trough anastrozole concentration. Further research is needed to verify whether this interaction affects treatment efficacy and to determine the pharmacological mechanism by which this interaction occurs.

AB - Aims: In the SWOG S0226 trial the combination of anastrozole plus fulvestrant (n = 349) was superior to anastrozole alone (n = 345) in hormone receptor (HR)-positive metastatic breast cancer. Here we report a pharmacokinetic subset analysis investigating a possible drug interaction between anastrozole and fulvestrant. Methods: Post-menopausal patients with HR-positive metastatic breast cancer were randomized to anastrozole with or without concurrent fulvestrant. Blood samples were collected at 2, 4, 6 and 8 months, just prior to receiving the next dose of anastrozole and fulvestrant. Drug concentrations were measured via LC/MS-MS. Anastrozole concentration was compared in patients on anastrozole alone vs. patients on concomitant fulvestrant. Comparisons were made at each time point using parametric tests and over time using a linear mixed effects model. Results: A total of 483 anastrozole concentration measurements were included, 224 samples from 64 patients on the anastrozole alone arm and 259 from 73 patients on the combination arm. The mean anastrozole concentration in the combination arm was significantly lower than that in the anastrozole alone arm at each sample collection time (all P <0.01) and in the mixed effects model (an estimated difference of 9.85 ng ml-1 (95% CI 5.69, 14.00 ng ml-1), P <0.001). Conclusion: A significant pharmacokinetic drug interaction was detected, in which the addition of fulvestrant to anastrozole treatment decreased the trough anastrozole concentration. Further research is needed to verify whether this interaction affects treatment efficacy and to determine the pharmacological mechanism by which this interaction occurs.

KW - Anastrozole

KW - Breast cancer

KW - Drug interaction

KW - Fulvestrant

KW - Pharmacokinetics

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