• Anne Aupérin, Cecile Le Péchoux, Estelle Rolland, Walter J Curran, Kiyoyuki Furuse, Pierre Fournel, Jose Belderbos, Gerald Clamon, Hakki Cuneyt Ulutin, Rebecca Paulus, Takeharu Yamanaka, Marie-Cecile Bozonnat, Apollonia Uitterhoeve, Xiaofei Wang, Lesley Stewart, Rodrigo Arriagada, Sarah Burdett, and Jean-Pierre Pignon.
• Unit of Biostatistics and Epidemiology, Institut Gustave-Roussy, 94805 Villejuif Cedex, France. auperin@igr.fr
• J. Clin. Oncol. 2010 May 1; 28 (13): 2181-90.

PurposeThe previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.MethodsSystematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity.ResultsOf seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity.ConclusionConcomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity.

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