Anastrozole and everolimus in advanced gynecologic and breast malignancies: activity and molecular alterations in the

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Jennifer J Wheler1, Stacy L Moulder2, Aung Naing

  • 1Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, TX.

Oncotarget
|June 11, 2014
PubMed
Abstract

Insights

Combining anastrozole with everolimus is safe and effective for heavily pretreated patients with hormone receptor-positive metastatic breast, ovarian, and endometrial cancers. This combination therapy showed antitumor activity, particularly in patients with PI3K/AKT/mTOR pathway alterations.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • PI3K/AKT/mTOR pathway activation can reduce hormone therapy effectiveness.
  • Investigating combination therapy to overcome resistance.

Purpose of the Study:

  • Evaluate safety and efficacy of anastrozole plus everolimus.
  • Assess antitumor activity and molecular correlates in metastatic ER/PR-positive cancers.

Main Methods:

  • Phase II trial of 55 patients with metastatic breast, ovarian, and endometrial tumors.
  • Administered anastrozole (1 mg daily) and everolimus (10 mg daily).
  • Monitored safety, antitumor response, and molecular alterations.

Main Results:

  • Combination therapy was well tolerated at full doses.
  • 24% of patients achieved stable disease (≥6 months), partial response, or complete response.
  • Responses were observed in patients with PI3K/AKT/mTOR pathway alterations and other molecular aberrations.

Conclusions:

  • Anastrozole and everolimus combination is safe and active in heavily pretreated patients.
  • Effective in ER/PR-positive breast, ovarian, and endometrial cancers.
  • Responses seen in patients with diverse molecular alterations.

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