title: A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer.
abstract: BACKGROUND
  The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive (HER2+), locally advanced/metastatic breast cancer and prior trastuzumab treatment.
  
  
  METHODS
  Patients received neratinib 240 mg/d continuously (n=117) or lapatinib 1250 mg/d continuously plus capecitabine 2000 mg/m(2) per day on days 1-14 of each 21-d cycle (n=116). The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival (PFS).
  
  
  RESULTS
  The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine (hazard ratio, 1.19; 95% confidence interval, 0.89-1.60; non-inferiority margin, 1.15). Median PFS for neratinib was 4.5 months versus 6.8 months for lapatinib plus capecitabine and median overall survival was 19.7 months versus 23.6 months. Objective response rate (neratinib, 29% versus lapatinib plus capecitabine, 41%; P=0.067) and clinical benefit rate (44% versus 64%; P=0.003) were lower for the neratinib arm but consistent with previously reported results. In both treatment arms, diarrhoea was the most frequently reported treatment-related adverse event of any grade (neratinib, 85% versus lapatinib plus capecitabine, 68%; P=0.002) and of grade 3/4 (28% versus 10%; P<0.001), but was typically managed with concomitant anti-diarrhoeal medication and/or study treatment modification. Importantly, neratinib had no significant skin toxicity.
  
  
  CONCLUSIONS
  The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated. The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2+ advanced breast cancer.
authors: Hospital Universitario Gregorio Marañón, Universidad Complutense, Calle de Maiquez 7, 28009 Madrid, Spain.
authors: Miguel
authors: M
authors: Martin
authors: Jacques
authors: J
authors: Bonneterre
authors: Charles E
authors: CE
authors: Geyer
authors: Yoshinori
authors: Y
authors: Ito
authors: Jungsil
authors: J
authors: Ro
authors: Istvan
authors: I
authors: Lang
authors: Sung-Bae
authors: SB
authors: Kim
authors: Caroline
authors: C
authors: Germa
authors: Jennifer
authors: J
authors: Vermette
authors: Kenneth
authors: K
authors: Wang
authors: Kongming
authors: K
authors: Wang
authors: Ahmad
authors: A
authors: Awada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D011804:Quinolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C487932:neratinib
keywords: Breast; phase II