Predictive Factors of Lapatinib and Capecitabine Activity in Patients with HER2-Positive, Trastuzumab-Resistant Metastatic Breast Cancer: Results from the Italian Retrospective Multicenter HERLAPAC Study

PLoS One. 2016 May 25;11(5):e0156221. doi: 10.1371/journal.pone.0156221. eCollection 2016.

Abstract

Background: There are no validated predictive markers for lapatinib and capecitabine in patients with trastuzumab-resistant HER2 positive metastatic breast cancer.

Methods: Data of 148 consecutive patients treated with lapatinib and capecitabine from March 2007 to December 2013 were collected from 13 Italian institutions. Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with logrank test. The association of clinicopathological variables and the outcome was studied by binary logistic regression analysis and Cox proportional hazard analysis.

Results: At a median follow-up of 41 months, median PFS and OS were 7 and 21 months, respectively. Patents with a PFS longer than 7 months had a significantly longer OS, compared with patients with a PFS equal to or shorter than 7 months (36 vs 15 months; p<0.001). Multivariate analysis revealed the benefit of lapatinib-based therapy in terms of PFS and OS was significantly associated with time-to-progression (TTP) on prior first-line trastuzumab-based therapy. In particular, each additional month on first-line trastuzumab based therapy was associated with a reduction in hazard of progression and death after the initiation of lapatinib-based therapy of 2% and 4%, respectively.

Conclusions: A longer TTP to first line trastuzumab seems to predict a prolonged PFS and OS with subsequent lapatinib and capecitabine.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Capecitabine / administration & dosage*
  • Capecitabine / pharmacology
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Italy
  • Lapatinib
  • Logistic Models
  • Middle Aged
  • Neoplasm Metastasis
  • Quinazolines / administration & dosage*
  • Quinazolines / pharmacology
  • Receptor, ErbB-2 / genetics*
  • Retrospective Studies
  • Survival Analysis
  • Trastuzumab
  • Young Adult

Substances

  • Quinazolines
  • Lapatinib
  • Capecitabine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab

Grants and funding

F. Montemurro is supported by Fondazione Piemontese per la Ricerca sul Cancro (ONLUS) 5 X 1000 Fondi Ministero della Salute 2012 - http://www.fprconlus.it/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.