Originally published as JCO Early Release 10.1200/JCO.2006.07.5754 on January 16 2007

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Phase II Clinical Trial of Chemotherapy-Naïve Patients 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer

David M. Jackman, Beow Y. Yeap, Neal I. Lindeman, Panos Fidias, Michael S. Rabin, Jennifer Temel, Arthur T. Skarin, Matthew Meyerson, Alison J. Holmes, Ana M. Borras, Boris Freidlin, Patricia A. Ostler, Joan Lucca, Thomas J. Lynch, Bruce E. Johnson, Pasi A. Jänne

From the Dana-Farber Cancer Institute; Brigham and Women’s Hospital; Massachusetts General Hospital; and Harvard Medical School, Boston, MA

Address reprint requests to Pasi A. Jänne, MD, PhD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: pjanne{at}partners.org

Purpose This is a phase II, multicenter, open-label study of chemotherapy-naïve patients with non–small-cell lung cancer (NSCLC) and age 70 years who were treated with erlotinib and evaluated to determine the median, 1-year, and 2-year survival. The secondary end points include radiographic response rate, time to progression (TTP), toxicity, and symptom improvement.

Patients and Methods Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity. Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors. Tumor samples were analyzed for the presence of somatic mutations in EGFR and KRAS.

Results Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005. There were eight partial responses (10%), and an additional 33 patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5 months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95% CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%, respectively. The most common toxicities were acneiform rash (79%) and diarrhea (69%). Four patients developed interstitial lung disease of grade 3 or higher, with one treatment-related death. EGFR mutations were detected in nine of 43 patients studied. The presence of an EGFR mutation was strongly correlated with disease control, prolonged TTP, and survival.

Conclusion Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.

published online ahead of print at www.jco.org on January 16, 2007.

Supported by Grants No. 1K12CA87723-01 (P.A.J.) and 1RO1CA114465-01 (B.E.J. and P.A.J.) from the National Institutes of Health, Grant No. P20CA90578-02 (B.E.J. and B.Y.Y) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc, as well as by the Doris and William Krupp Research Fund in Thoracic Oncology.

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

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