Triple-negative breast cancer patients treated at MD Anderson Cancer Center in phase I trials: improved outcomes with combination chemotherapy and targeted agents

Mol Cancer Ther. 2014 Dec;13(12):3175-84. doi: 10.1158/1535-7163.MCT-14-0358. Epub 2014 Sep 24.

Abstract

Patients with metastatic triple-negative breast cancer (TNBC) have poor treatment outcomes. We reviewed the electronic records of consecutive patients with metastatic TNBC treated in phase I clinic at MD Anderson Cancer Center (Houston, TX) between Augu st 2005 and May 2012. One hundred and six patients received at least 1 phase I trial. Twelve of 98 evaluable patients (12%) had either complete response (CR; n = 1), partial response (PR; n = 7), or stable disease ≥ 6 months (SD; n = 4). Patients treated on matched therapy (n = 16) compared with those on nonmatched therapy (n = 90) had improved SD ≥ 6 months/PR/CR (33% vs. 8%; P = 0.018) and longer progression-free survival (PFS; median, 6.4 vs. 1.9 months; P = 0.001). Eleven of 57 evaluable patients (19%) treated with combination chemotherapy and targeted therapy had SD ≥ 6 months/PR/CR versus 1 of 41 evaluable patients (2%) treated on other phase I trials (P = 0.013), and longer PFS (3.0 vs. 1.6 months; P < 0.0001). Patients with molecular alterations in the PI3K/AKT/mTOR pathway treated on matched therapy (n = 16) had improved PFS compared with those with and without molecular alterations treated on nonmatched therapy (n = 27; 6.4 vs. 3.2 months; P = 0.036). On multivariate analysis, improved PFS was associated with treatment with combined chemotherapy and targeted agents (P = 0.0002), ≤ 2 metastatic sites (P = 0.003), therapy with PI3K/AKT/mTOR inhibitors for those with cognate pathway abnormalities (P = 0.018), and treatment with antiangiogenic agents (P = 0.023). In summary, combinations of chemotherapy and angiogenesis and/or PI3K/AKT/mTOR inhibitors demonstrated improved outcomes in patients with metastatic TNBC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials, Phase I as Topic
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retrospective Studies
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Texas
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / mortality

Substances

  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases