title: Retreatment with trastuzumab after progression on lapatinib-based therapy in heavily pretreated HER2-positive metastatic breast cancer: a single-institution experience.
abstract: OBJECTIVE
  The study aimed to determine if retreatment with trastuzumab after progression on treatment with lapatinib is feasible in a previously heavily pretreated population of HER2-positive metastatic breast cancer patients and if some range of activity and an acceptable toxicity profile could be shown.
  
  
  METHODS
  Women with HER2-positive metastatic breast carcinoma whose disease progressed after antracycline, taxane and trastuzumab-based regimens were treated at progression with lapatinib plus capecitabine. At progression on this combination, retreatment with trastuzumab combined with different cytotoxic agents was offered to most patients. The outcome of these patients was evaluated.
  
  
  RESULTS
  Between April 2007 and February 2013, a total of 77 patients with HER2-positive metastatic breast cancer were identified who had been treated with lapatinib plus capecitabine at our institution. At progression, 43 (55%) were treated again with a trastuzumab-based regimen, mostly gemcitabine and vinorelbine. One complete response (CR) and 17 partial responses plus 4 prolonged stable periods longer than 6 months for a 51.1% overall clinical benefit were observed. No severe toxicities were encountered except one case of heart failure reported in a heavily antracycline-pretreated patient, who, however, recovered from this toxicity.
  
  
  CONCLUSIONS
  Even if our sample is a favorably selected population of HER2-positive patients responding to sequential targeted therapies, our data suggest that trastuzumab can be used again in association with a different cytotoxic agent in patients heavily pretreated with trastuzumab and after progression on lapatinib plus capecitabine, without any significant toxicity and with an encouraging clinical benefit rate, suggesting there is an opportunity to continue blockade of the HER2 receptor.
authors: Paolo
authors: P
authors: Carli
authors: Loredana
authors: L
authors: Militello
authors: Gian Maria
authors: GM
authors: Miolo
authors: Daniela
authors: D
authors: Quitadamo
authors: Davide
authors: D
authors: Lombardi
authors: Elena
authors: E
authors: Torrisi
authors: Simona
authors: S
authors: Scalone
authors: Diana
authors: D
authors: Crivellari
authors: Simon
authors: S
authors: Spazzapan
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D019233:Retreatment; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; C508053:ERBB2 protein, human