title: Triple-negative breast cancer patients treated at MD Anderson Cancer Center in phase I trials: improved outcomes with combination chemotherapy and targeted agents.
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.
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Prasanth
authors.initials: P
authors.lastname: Ganesan
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stacy
authors.initials: S
authors.lastname: Moulder
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Zinner
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Bettzy
authors.initials: B
authors.lastname: Stephen
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Philip
authors.initials: P
authors.lastname: Stephens
authors.affiliation: Foundation Medicine, Cambridge, Massachusetts.
authors.forename: Roman
authors.initials: R
authors.lastname: Yelensky
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Center for Personalized Cancer Therapy, Moores Cancer Center, The University of California San Diego, La Jolla, California.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas. jjwheler@mdanderson.org.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013781:Texas; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases