title: Randomized phase II study of weekly docetaxel plus trastuzumab versus weekly paclitaxel plus trastuzumab in patients with previously untreated advanced nonsmall cell lung carcinoma.
abstract: BACKGROUND
  Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor-2 (HER-2). Nonsmall cell lung carcinoma (NSCLC) overexpresses HER-2 protein in approximately 20% of cases. In the current study, the authors combined trastuzumab with weekly taxanes in an attempt to improve outcomes over standard chemotherapy in patients with advanced NSCLC.
  
  
  METHODS
  The primary objective was to determine whether docetaxel plus trastuzumab or paclitaxel plus trastuzumab was the superior regimen based on response and toxicity, and to determine whether either regimen was appropriate for further testing in a randomized Phase III trial. After stratification based on the results of HER-2 immunohistochemistry, chemotherapy-naive patients were randomized to receive trastuzumab plus docetaxel or trastuzumab plus paclitaxel. The study was designed so patients with or without HER-2 overexpression would be distributed equally between the study arms.
  
  
  RESULTS
  Immunohistochemistry for HER-2 protein expression was attempted for 182 pathologic samples from 169 patients. Twenty-eight of the 179 evaluable samples (16%) revealed 2+ or 3+ staining. The objective response rate was 23% (7 of 30 patients) in the patients treated with docetaxel plus trastuzumab and 32% (11 of 34 patients) in the patients treated with paclitaxel plus trastuzumab (P=0.76, Wilcoxon test). No difference was noted in the median survival (16 mos vs. 14 mos) or 1-year survival (57% vs. 55%) (P=0.998). Toxicities were mild in both treatment arms. No difference with regard to response rates or survival was noted between HER-2-positive (2+ or 3+) and HER-2-negative (0-1+) patients.
  
  
  CONCLUSIONS
  The expression of HER-2 protein in patients with advanced NSCLC in this study was found to be similar to that reported in previous series. The response rates and toxicities for patients treated with docetaxel and trasuzumab or paclitaxel and trasuzumab were not significantly different, though survival in both arms was better than expected. HER-2 expression status did not appear to affect outcomes for this uniform group of patients who were treated in a comparable fashion. Because of the infrequency of HER-2 overexpression, and the absence of improved outcomes in patients with NSCLC who were treated with trastuzumab plus chemotherapy in other studies, neither regimen tested will be advanced to a Phase III trial.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA. krugl@mskcc.org
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Jyoti
authors.initials: J
authors.lastname: Patel
authors.forename: John
authors.initials: J
authors.lastname: Crapanzano
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Jorge
authors.initials: J
authors.lastname: Gomez
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Robert T
authors.initials: RT
authors.lastname: Heelan
authors.forename: Barbara
authors.initials: B
authors.lastname: Pizzo
authors.forename: Leslie
authors.initials: L
authors.lastname: Tyson
authors.forename: Christine
authors.initials: C
authors.lastname: Sheehan
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000077143:Docetaxel; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab