The influence of sex and histology on outcomes in non-small-cell lung cancer: a pooled analysis of five randomized trials.

BACKGROUND Some non-small-cell lung cancer (NSCLC) surgical series have indicated that the positive prognostic effect of female sex is limited to patients with adenocarcinoma. We carried out a retrospective analysis to investigate the role of sex and histology on efficacy, toxicity, and dose delivery after chemotherapy. PATIENT AND METHODS Individual patient data were pooled from five randomized, phase III, advanced NSCLC chemotherapy trials. Primary outcomes were response rate, overall survival (OS), toxicity, and dose delivery. A secondary analysis examined survival by sex in histological subgroups. RESULTS Of 2349 patients, 34% were women. Women had a higher response rate to chemotherapy (42% versus 40%, P = 0.01) and longer survival than men (median OS 9.6 versus 8.6 months, P = 0.002). The difference in OS remained after adjusting for age, stage, performance status, and histology (hazard ratio 0.83, 95% confidence interval 0.74-0.92, P = 0.0005). Upon further examination, longer survival in women was only seen in patients with adenocarcinoma (test for interaction P = 0.006). There were no differences in hematological toxicity or transfusions. Women experienced more grade 3-4 emesis than men (P < 0.0001) and more dose delays (P = 0.02) or dose reductions (P < 0.0001). CONCLUSION The positive prognostic effect among women is confirmed in patients receiving platinum-based chemotherapy but appears confined to those with adenocarcinoma histology.

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