Originally published as JCO Early Release 10.1200/JCO.2007.13.9030 on May 27 2008

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Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group

Jean-Pierre Pignon, Hélène Tribodet, Giorgio V. Scagliotti, Jean-Yves Douillard, Frances A. Shepherd, Richard J. Stephens, Ariane Dunant, Valter Torri, Rafael Rosell, Lesley Seymour, Stephen G. Spiro, Estelle Rolland, Roldano Fossati, Delphine Aubert, Keyue Ding, David Waller, Thierry Le Chevalier

From the Institut Gustave-Roussy, Villejuif; Centre René Gauducheau, St-Herblain; Pierre Fabre Oncology, Boulogne, France; University of Torino, Torino; Mario Negri Institute, Milano, Italy; University Health Network, Princess Margaret Hospital, Toronto; National Cancer Institute of Canada, Kingston, Ontario, Canada; Medical Research Council Clinical Trials Unit; University College Hospital, London; Glenfield Hospital, Leicester, United Kingdom; and Catalan Institute of Oncology, Badalona, Spain

Corresponding author: Jean-Pierre Pignon, MD, PhD, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France; e-mail: jppignon{at}igr.fr

Purpose: Several recent trials have shown a significant overall survival (OS) benefit from postoperative cisplatin-based chemotherapy in patients with non–small-cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation was to identify treatment options associated with a higher benefit or groups of patients who particularly benefit from postoperative chemotherapy.

Patients and Methods: Individual patient data were collected and pooled from the five largest trials (4,584 patients) of cisplatin-based chemotherapy in completely resected patients that were conducted after the 1995 NSCLC meta-analysis. The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analyzed using hazard ratios (HRs) and log-rank tests stratified by trial.

Results: With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, P = .04; HR for stage IA = 1.40; 95% CI, 0.95 to 2.06; HR for stage IB = 0.93; 95% CI, 0.78 to 1.10; HR for stage II = 0.83; 95% CI, 0.73 to 0.95; and HR for stage III = 0.83; 95% CI, 0.72 to 0.94). The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR = 0.80; 95% CI, 0.70 to 0.91), etoposide or vinca alkaloid (HR = 0.92; 95% CI, 0.80 to 1.07), or other (HR = 0.97; 95% CI, 0.84 to 1.13). Chemotherapy effect was higher in patients with better performance status. There was no interaction between chemotherapy effect and sex, age, histology, type of surgery, planned radiotherapy, or planned total dose of cisplatin.

Conclusion: Postoperative cisplatin-based chemotherapy significantly improves survival in patients with NSCLC.

published online ahead of print at www.jco.org on May 27, 2008.

Supported by Institut Gustave-Roussy, Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le Cancer, Sanofi-Aventis (unrestricted grants), and Pierre Fabre Oncology (unrestricted grants).

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Members of the Lung Adjuvant Cisplatin Evaluation Collaborative Group are listed in the Appendix (online only).

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

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