Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: A phase III trial - INTACT 2

Roy S. Herbst, Giuseppe Giaccone, Joan H. Schiller, Ronald B. Natale, Vincent Miller, Christian Manegold, Giorgio Scagliotti, Rafael Rosell, Ira Oliff, James A. Reeves, Michael K. Wolf, Annetta D. Krebs, Steven D. Averbuch, Judith S. Ochs, John Grous, Abderrahim Fandi, David H. Johnson

Research output: Contribution to journalArticlepeer-review

1664 Scopus citations


Purpose: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. Patients and Methods: Patients received paclitaxel 225 mg/m2 and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results: A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P = .64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received ≥ 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. Conclusion: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.

Original languageEnglish (US)
Pages (from-to)785-794
Number of pages10
JournalJournal of Clinical Oncology
Issue number5
StatePublished - 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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