title: Phase II study on lapatinib in advanced EGFR-positive chordoma.
abstract: BACKGROUND
  To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients.
  
  
  METHODS
  From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months).
  
  
  RESULTS
  All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR.
  
  
  CONCLUSIONS
  This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.
authors.affiliation: Sarcoma Unit, Departments of Cancer Medicine. Electronic address: silvia.stacchiotti@istitutotumori.mi.it.
authors.forename: S
authors.initials: S
authors.lastname: Stacchiotti
authors.affiliation: Pathology, Laboratory of Molecular Pathology.
authors.forename: E
authors.initials: E
authors.lastname: Tamborini
authors.affiliation: Unit of Clinical Epidemiology and Trial Organization.
authors.forename: S
authors.initials: S
authors.lastname: Lo Vullo
authors.affiliation: Pathology, Laboratory of Molecular Pathology.
authors.forename: F
authors.initials: F
authors.lastname: Bozzi
authors.affiliation: Departments of Radiology.
authors.forename: A
authors.initials: A
authors.lastname: Messina
authors.affiliation: Departments of Radiology.
authors.forename: C
authors.initials: C
authors.lastname: Morosi
authors.affiliation: Departments of Radiology.
authors.forename: A
authors.initials: A
authors.lastname: Casale
authors.affiliation: Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: F
authors.initials: F
authors.lastname: Crippa
authors.affiliation: Pathology, Laboratory of Molecular Pathology.
authors.forename: E
authors.initials: E
authors.lastname: Conca
authors.affiliation: Pathology, Laboratory of Molecular Pathology.
authors.forename: T
authors.initials: T
authors.lastname: Negri
authors.affiliation: Sarcoma Unit, Departments of Cancer Medicine.
authors.forename: E
authors.initials: E
authors.lastname: Palassini
authors.affiliation: Sarcoma Unit, Departments of Cancer Medicine.
authors.forename: A
authors.initials: A
authors.lastname: Marrari
authors.affiliation: Chemotherapy Unit, Istituto Ortopedico Rizzoli, Bologna.
authors.forename: E
authors.initials: E
authors.lastname: Palmerini
authors.affiliation: Unit of Clinical Epidemiology and Trial Organization.
authors.forename: L
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gronchi
authors.affiliation: Pathology, Laboratory of Molecular Pathology.
authors.forename: S
authors.initials: S
authors.lastname: Pilotti
authors.affiliation: Sarcoma Unit, Departments of Cancer Medicine.
authors.forename: P G
authors.initials: PG
authors.lastname: Casali
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002817:Chordoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D012447:Sacrum / Q000473:pathology; D019291:Skull Base / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077341:Lapatinib; D066246:ErbB Receptors
keywords: EGFR; chemotherapy; chordoma; lapatinib; sarcoma; tyrosine kinase