title: A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer.
abstract: BACKGROUND
  Pertuzumab plus trastuzumab provides a more comprehensive blockade of HER2 signalling than trastuzumab alone. Therefore, we conducted a phase IIa study of the pharmacokinetics and safety of pertuzumab plus trastuzumab and chemotherapy in advanced gastric cancer (aGC).
  
  
  METHODS
  Patients received pertuzumab 840 mg for cycle 1 and 420 mg q3w for cycles 2-6 (Arm A) or pertuzumab 840 mg q3w for six cycles (Arm B). Trastuzumab, cisplatin and capecitabine were also given for six cycles, then trastuzumab q3w until disease progression or unmanageable toxicity. The co-primary endpoints were day 43 pertuzumab serum trough concentration (Cmin) and safety.
  
  
  RESULTS
  Thirty patients were randomised. Mean pertuzumab Cmin at day 43 was 40.0 μg ml(-1) (s.d.: 17.3) in Arm A and 62.7 μg ml(-1) (29.1) in Arm B. Mean day 43 Cmin in Arm A was ~37% lower than that seen in metastatic breast cancer. The safety profiles were similar between arms and treatment was well tolerated. Partial responses were achieved by 86% and 55% of patients in Arms A and B, respectively.
  
  
  CONCLUSIONS
  On the basis of the pharmacokinetic and safety data, the 840 mg q3w pertuzumab dose has been selected for a phase III study of pertuzumab, trastuzumab and chemotherapy in HER2-positive aGC.
authors: Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul 138-736, Korea.
authors: Y-K
authors: YK
authors: Kang
authors: Yonsei Cancer Center, Yonsei Cancer Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors: S Y
authors: SY
authors: Rha
authors: Medical Oncology Unit, Magna Graecia University, Viale Europa, 88100 Catanzaro, Italy.
authors: P
authors: P
authors: Tassone
authors: Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors: J
authors: J
authors: Barriuso
authors: Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors: R
authors: R
authors: Yu
authors: Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors: T
authors: T
authors: Szado
authors: Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors: A
authors: A
authors: Garg
authors: Seoul National University College of Medicine, 01 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Y-J
authors: YJ
authors: Bang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D002945:Cisplatin; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab