title: 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.
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.
authors.affiliation: Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.affiliation: Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Inno
authors.affiliation: Medical Oncology, Ospedale Civile di Saluzzo, Saluzzo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossi
authors.affiliation: Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Turazza
authors.affiliation: Medical Oncology, AO Universitaria Integrata Verona, Verona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Fiorio
authors.affiliation: Medical Oncology A, INT Regina Elena, Roma, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.affiliation: Medical Oncology, IRCCS AO S.Maria Nuova, Reggio Emilia, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bisagni
authors.affiliation: Medical Oncology, S.Maria della Misericordia Hospital, Perugia, Italy.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Foglietta
authors.affiliation: Medical Oncology, Università Campus Biomedico, Roma, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Medical Oncology, San Pietro Fatebenefratelli Hospital, Roma, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Pavese
authors.affiliation: Medical Oncology, San Pietro Fatebenefratelli Hospital, Roma, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Pellegrino
authors.affiliation: Medical Oncology, IRCCS Fondazione S. Maugeri, Pavia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zambelli
authors.affiliation: Medical Oncology B - INT Regina Elena, Roma, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.affiliation: Medical Oncology, ARNAS Civico, Palermo, Italy.
authors.forename: Vita
authors.initials: V
authors.lastname: Leonardi
authors.affiliation: Medical Oncology, AO Treviglio - Bergamo, Bergamo, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.affiliation: Medical Oncology, S.Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Saracchini
authors.affiliation: Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bogina
authors.affiliation: Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Marchetti
authors.affiliation: Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Duranti
authors.affiliation: Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Lunardi
authors.affiliation: Investigative Clinical Oncology (INCO), Fondazione del Piemonte per L'Oncologia, Candiolo Cancer Institute (IRCCS), Candiolo, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000069287:Capecitabine / Q000008:administration & dosage* / Q000494:pharmacology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D007558:Italy; D000077341:Lapatinib; D016015:Logistic Models; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D000068878:Trastuzumab; D055815:Young Adult
chemical_list: D000069287:Capecitabine; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human