Faculty Collaboration Database

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

Date

09/26/2014

Pubmed ID

25253784

Pubmed Central ID

PMC4258414

DOI

10.1158/1535-7163.MCT-14-0358

Scopus ID

2-s2.0-84918500160 (requires institutional sign-in at Scopus site)   30 Citations

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.

Author List

Ganesan P, Moulder S, Lee JJ, Janku F, Valero V, Zinner RG, Naing A, Fu S, Tsimberidou AM, Hong D, Stephen B, Stephens P, Yelensky R, Meric-Bernstam F, Kurzrock R, Wheler JJ

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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