Journal of Clinical Oncology, Vol 25, No 12 (April 20), 2007: pp. 1545-1552
© 2007 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2005.05.1474
Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial
Ulrich Gatzemeier,
Anna Pluzanska,
Aleksandra Szczesna,
Eckhard Kaukel,
Jaromir Roubec,
Flavio De Rosa,
Janusz Milanowski,
Hanna Karnicka-Mlodkowski,
Milos Pesek,
Piotr Serwatowski,
Rodryg Ramlau,
Terezie Janaskova,
Johan Vansteenkiste,
Janos Strausz,
Georgy Moiseevich Manikhas,
Joachim Von Pawel
From the Zentrum Fur Pneumologie Und Thoraxchirurgie, Krankenhaus D LVA; Pneumology, Hospital Harburg, Hamburg; Asklepios Fachkliniken Muenchen-Gauting, Onkologie, Gauting, Germany; Chemotherapy Clinic, Medical Academy of Lodz, Lodz; Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy, Oddzial III, Otwock; Akademia Medyczna W Lublinie, Karedra I Klinika Chorob Pluc, Lublin; Oddzial Chemioterapii, Szpital Morski Im. Pck, Gdynia; Specjalistyczny Szpital Im., Oddzial Chemioterapii, Szczecin; Wielkopolskie Centrum Chorób P uc i Gru licy, Pozna Poland; Klinika TBC a Respiracnich Onemocneni, Ostrava-Poruba, Czech Republic; F. Hoffmann-La Roche, Basel, Switzerland; Fakultni Nemocnice V Plzni, Plicni Klinika, Plzen; Vitkovicka Nemocnice Bma A.S., Plicni Oddeleni, Ostrava, Czech Republic; Department of Pulmonary Medicine, Universitair Ziekenhuis Leuven, Leuven, Belgium; 2nd Department of Pulmonary Medicine, Institute of Pulmonary Medicine Torokbalint, Torokbalint, Hungary; and the Pulmonary Department, St Petersburg City Oncological Dispensary, St Petersburg, Russian Federation
Address reprint requests to Ulrich Gatzemeier, MD, Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany; e-mail: pneumo.onko{at}t-online.de
Purpose Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non–small-cell lung cancer (NSCLC).
Patients and Methods Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL).
Results A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild).
Conclusion Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.
Supported by F. Hoffmann-La Roche Ltd.
Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA.
Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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