Originally published as JCO Early Release 10.1200/JCO.2007.14.4824 on March 31 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Kelly, K. Articles by Gandara, D. R. PubMed PubMed Citation Articles by Kelly, K. Articles by Gandara, D. R. Related Articles Related Editorial

Phase III Trial of Maintenance Gefitinib or Placebo After Concurrent Chemoradiotherapy and Docetaxel Consolidation in Inoperable Stage III Non–Small-Cell Lung Cancer: SWOG S0023

Karen Kelly, Kari Chansky, Laurie E. Gaspar, Kathy S. Albain, James Jett, Yee C. Ung, Derick H.M. Lau, John J. Crowley, David R. Gandara

From the University of Kansas Medical Center, Kansas City, MO; Southwest Oncology Group Statistical Center, Seattle, WA; University of Colorado Health Sciences Center, Denver, CO; Loyola University School of Medicine, Maywood, IL; Mayo Clinic Rochester, Rochester, MN; University of California at Davis, Sacramento, CA; and Toronto-Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada

Corresponding author: Karen Kelly, MD, University of Kansas Medical Center, 4030 Robinson Hall, Mail Stop 1027, 3901 Rainbow Blvd, Kansas City, KS 66160; e-mail: kkelly{at}kumc.edu

Purpose: Early clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non–small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease.

Patients and Methods: Untreated patients with stage III NSCLC, a performance score of 0 to 1, and adequate organ function were eligible. All patients received cisplatin 50 mg/m² on days 1 and 8 plus etoposide 50 mg/m² on days 1 to 5, every 28 days for two cycles with concurrent thoracic radiation (1.8- to 2-Gy fractions per day; total dose, 61 Gy) followed by three cycles of docetaxel 75 mg/m². Patients whose disease did not progress were randomly assigned to gefitinib 250 mg/d or placebo until disease progression, intolerable toxicity, or the end of 5 years. The planned sample size was 672 patients to confer power of 0.89 to detect a 33% increase over the expected median survival time of 21 months (one-sided P = .025, log-rank test). Random assignment was stratified by stage, histology, and measurable versus nonmeasurable disease.

Results: Enrollment began in July 2001. An unplanned interim analysis conducted in April 2005 rejected the alternative hypothesis of improved survival at the P = .0015 level for 243 randomly assigned patients. The study closed, and preliminary results were reported. Now, with a median follow-up time of 27 months, median survival time was 23 months for gefitinib (n = 118) and 35 months for placebo (n = 125; two-sided P = .013). The toxic death rate was 2% with gefitinib compared with 0% for placebo.

Conclusion: In this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity.

published online ahead of print at www.jco.org on March 31, 2008.

Supported in part by AstraZeneca and Sanofi-aventis and the following National Cancer Institute, Department of Health and Human Services, Public Health Service Cooperative Agreement Grants No.: CA38926, CA32102, CA46441, CA35431, CA37663, CA46282, CA35261, CA14028, CA35119, CA45377, CA35178, CA45450, CA42777, CA67575, CA20319, CA04919, CA35090, CA46368, CA35176, CA45808, CA45560, CA35192, CA52654, CA63844, CA35281, CA45807, CA35128, CA35262, CA63845, CA74647, CA86780, CA63850, CA13612, CA45461, CA63848, CA11083, CA58882, and CA74811.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Editorial

• Does Gefitinib Shorten Lung Cancer Survival? Chaos Redux
  Vicki L. Keedy, Carlos L. Arteaga, and David H. Johnson
  JCO 2008 26: 2428-2430 [Full Text]

This article has been cited by other articles:

				V. L. Keedy, C. L. Arteaga, and D. H. Johnson Does Gefitinib Shorten Lung Cancer Survival? Chaos Redux J. Clin. Oncol., May 20, 2008; 26(15): 2428 - 2430. [Full Text] [PDF]