Originally published as JCO Early Release 10.1200/JCO.2008.21.5541 on September 8 2009

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Randomized, Placebo-Controlled, Phase II Study of Sequential Erlotinib and Chemotherapy As First-Line Treatment for Advanced Non–Small-Cell Lung Cancer

From The Chinese University of Hong Kong, Sir YK Pau Cancer Center, State Key Laboratory of Southern China, Prince of Wales Hospital; Roche Hong Kong, Hong Kong; Guangdong General Hospital; Cancer Center of Sun Yat-Sen University, Guangzhou; Shanghai Pulmonary Hospital; Shanghai Chest Hospital, Shanghai; China; National Taiwan University Hospital; Taipei Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Philippine General Hospital; Cardinal Santos Medical Center, Manila, Philippines; Faculty of Medicine, Siriraj Hospital, Mahidol University; The King Chulalongkorn Memorial Hospital and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Sydney Cancer Centre; Roche Products, Sydney, Australia; Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; National Cancer Center, Goyang, Gyeonggi, South Korea.

Corresponding author: Jin-Soo Lee, MD, 111 Jungbalsan-ro, Ilsadong-gu, Goyang-si, Gyeonggi-do, Republic of Korea; e-mail: jslee{at}ncc.re.kr.

Purpose This study investigated whether sequential administration of erlotinib and chemotherapy improves clinical outcomes versus chemotherapy alone in unselected, chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC).

Patients and Methods Previously untreated patients (n = 154) with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive erlotinib (150 mg/d) or placebo on days 15 to 28 of a 4-week cycle that included gemcitabine (1,250 mg/m² days 1 and 8) and either cisplatin (75 mg/m² day 1) or carboplatin (5 x area under the serum concentration-time curve, day 1). The primary end point was nonprogression rate (NPR) at 8 weeks. Secondary end points included tumor response rate, NPR at 16 weeks, duration of response, progression-free survival (PFS), overall survival (OS), and safety.

Results The NPR at 8 weeks was 80.3% in the gemcitabine plus cisplatin or carboplatin (GC) -erlotinib arm (n = 76) and 76.9% in the GC-placebo arm (n = 78). At 16 weeks, the NPR was 64.5% for GC-erlotinib versus 53.8% for GC-placebo. The response rate was 35.5% for GC-erlotinib versus 24.4% for GC-placebo. PFS was significantly longer with GC-erlotinib than with GC-placebo (adjusted hazard ratio, 0.47; log-rank P = .0002; median, 29.4 v 23.4 weeks); this benefit was consistent across all clinical subgroups. There was no significant difference in OS. The addition of erlotinib to chemotherapy was well tolerated, with no increase in hematologic toxicity, and no treatment-related interstitial lung disease.

Conclusion Sequential administration of erlotinib following gemcitabine/platinum chemotherapy led to a significant improvement in PFS. This treatment approach warrants further investigation in a phase III study.

Supported by F. Hoffmann-La Roche, Basel, Switzerland.

Presented in part as a poster discussion at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL, and as an oral presentation at the 2008 University of Chicago-IASLC-ASCO-ASTRO (International Association for the Study of Lung Cancer-American Society of Clinical Oncology-American Society for Radiation Oncology) Chicago Multidisciplinary Symposium in Thoracic Oncology, November 13-15, 2008, Chicago, IL.

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

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