title: Trastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Metastatic Breast Cancer Previously Treated With Chemotherapy and 2 or More HER2-Targeted Agents: Results From the T-PAS Expanded Access Study.
abstract: OBJECTIVE
  The antibody-drug conjugate trastuzumab emtansine (T-DM1) has improved outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), as demonstrated in phase III studies. Few data approximating its use in routine clinical practice are available.
  
  
  METHODS
  The T-DM1 Patient Access Study was an expanded-access, multicenter study of T-DM1 in US patients with pretreated HER2-positive locally advanced breast cancer or MBC. The primary endpoint was safety. The secondary endpoint was investigator-assessed objective response rate among patients with measurable disease at baseline. Data are presented for the first 215 enrolled patients.
  
  
  RESULTS
  The median number of prior systemic MBC agents was 8 (range, 3-23). At baseline, median left ventricular ejection fraction was 60%, and 52.6% of patients had nonclinically significant cardiovascular disease. Median T-DM1 treatment duration was 5.0 months (range, 0-29 months; median follow-up, 5.9 months), with 18.6% having received more than 18 cycles. The most common any-grade adverse events were fatigue (50.7%) and nausea (38.1%). Adverse events of grade 3 or greater were reported in 46.5%, most commonly thrombocytopenia and platelet count decrease (10.2%). Bleeding of grade 3 or greater was reported in 4 patients (1.9%). Cardiac dysfunction (primarily asymptomatic left ventricular ejection fraction decreases) was reported in 14 patients (6.5%). Among those with measurable disease at baseline (n = 172), objective response rate was 25.6% (95% confidence interval, 19.2%-32.8%).
  
  
  CONCLUSIONS
  The safety profile of T-DM1 in this real-world setting of heterogeneous, HER2-positive, pretreated, locally advanced breast cancer or MBC was comparable with that reported in phases II and III studies of similar patient populations. T-DM1 was efficacious with no new safety signals.
authors.affiliation: From the *Breast Cancer Research, Sarah Cannon Research Institute; and †Medical Oncology, Tennessee Oncology, PLLC, Nashville, TN; ‡Dana-Farber Cancer Institute, Boston, MA; §Smilow Cancer Center, Yale University, New Haven, CT; ∥AdvancedBC.org, New York, NY; ¶Genentech, Inc, South San Francisco, CA; and #Mayo Clinic, Jacksonville, FL.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Ian E
authors.initials: IE
authors.lastname: Krop
authors.forename: Patricia M
authors.initials: PM
authors.lastname: LoRusso
authors.forename: Musa
authors.initials: M
authors.lastname: Mayer
authors.forename: Brian
authors.initials: B
authors.lastname: Barnett
authors.forename: Bongin
authors.initials: B
authors.lastname: Yoo
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy / Q000473:pathology; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008453:Maytansine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019233:Retreatment; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab