title: Sunitinib in combination with trastuzumab for the treatment of advanced breast cancer: activity and safety results from a phase II study.
abstract: BACKGROUND
  This phase II study evaluated the efficacy and safety/tolerability of sunitinib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC).
  
  
  METHODS
  Eligible patients received sunitinib 37.5 mg/day and trastuzumab administered either weekly (loading, 4 mg/kg; then weekly 2 mg/kg) or 3-weekly (loading, 8 mg/kg; then 3-weekly 6 mg/kg). Prior trastuzumab and/or lapatinib treatment were permitted. The primary endpoint was objective response rate (ORR).
  
  
  RESULTS
  Sixty patients were enrolled and evaluable for safety; 57 were evaluable for efficacy. The majority of patients (58%) had received no prior chemotherapy in the metastatic setting. The ORR was 37%; the clinical benefit rate (CBR; percent objective response plus stable disease ≥ 24 weeks) was 56%. Among patients who were treatment-naïve or had received only adjuvant therapy, the ORR was 44% and the CBR was 59%. Overall, median overall survival had not been reached and the 1-year survival rate was 91%. The majority of adverse events (AEs) were mild to moderate in severity. Forty percent of patients experienced AEs related to measured left ventricular ejection fraction (LVEF) declines, which occurred more frequently in patients who had received prior anthracycline treatment. Ten percent of patients exhibited symptoms related to LVEF declines. One patient died on study from cardiogenic shock. Antitumor response and several safety parameters appeared to correlate with sunitinib exposure.
  
  
  CONCLUSIONS
  Sunitinib plus trastuzumab demonstrated antitumor activity in patients with HER2-positive ABC, particularly those who were treatment-naïve or had only received prior adjuvant treatment. Sunitinib plus trastuzumab had acceptable safety and tolerability in patients with HER2-positive ABC who had not received prior anthracycline therapy.
  
  
  BACKGROUND
  NCT00243503.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garcia-Saenz
authors.forename: Sunil
authors.initials: S
authors.lastname: Verma
authors.forename: Maya
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.forename: Mark F
authors.initials: MF
authors.lastname: Kozloff
authors.forename: Catherine
authors.initials: C
authors.lastname: Prady
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Reza
authors.initials: R
authors.lastname: Khosravan
authors.forename: Zhixiao
authors.initials: Z
authors.lastname: Wang
authors.forename: Rossano
authors.initials: R
authors.lastname: Cesari
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tassell
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kern
authors.affiliation: EORTC, Soft Tissue and Bone Sarcoma Group, Centre Léon-Bérard and Université Claude Bernard, Lyon, France. jean-yves.blay@lyon.unicancer.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D011758:Pyrroles; D000068878:Trastuzumab; D000077210:Sunitinib