title: Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.
abstract: BACKGROUND
  The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.
  
  
  METHODS
  All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services' (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model.
  
  
  RESULTS
  64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5-16.5) vs. 31.0 for TBP (95% CI: 20.6-41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40-0.99, P = 0.045].
  
  
  CONCLUSIONS
  In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.
authors.affiliation: Chief Physician's Office, Clalit Health Services Headquarters, Tel-Aviv, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Hammerman
authors.affiliation: Chief Physician's Office, Clalit Health Services Headquarters, Tel-Aviv, Israel.
authors.forename: Sari
authors.initials: S
authors.lastname: Greenberg-Dotan
authors.affiliation: Chief Physician's Office, Clalit Health Services Headquarters, Tel-Aviv, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Feldhamer
authors.affiliation: Chief Physician's Office, Clalit Health Services Headquarters, Tel-Aviv, Israel; The Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Bitterman
authors.affiliation: Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Rinat
authors.initials: R
authors.lastname: Yerushalmi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007557:Israel / Q000453:epidemiology; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D000068878:Trastuzumab / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human