An Analysis of the Influence of Sex and Histology on Outcomes in Non-Small Cell Lung Cancer

BackgroundFemale sex is a modest positive prognostic factor in non-small cell lung cancer (NSCLC), in both early and late-stage disease. Some surgical series have suggested this benefit is limited to adenocarcinoma patients. We performed a retrospective analysis to investigate the role of sex and histology on efficacy, toxicity and dose delivery.MethodsIndividual patient data from five randomized phase III NSCLC trials, investigating platinum-based first-line chemotherapy regimens, were pooled in a single database and analyzed by patient sex. Primary outcomes were tumor response rate, overall survival (OS), lung cancer specific survival (LCSS), hematological and non-hematological toxicity and dose delivery. A secondary analysis examined survival by sex in histological subgroups. ResultsOf 2349 patients included, 793 were women (34%). Baseline demographics are shown in the Table. Overall, women had a higher response rate to chemotherapy (44% versus 39%, p=0.007), and longer survival than men (median OS 9.6 versus 8.6 months, one-year survival 41% versus 35%, HR 0.86 [95% CI 0.78-0.95], p=0.002; median LCSS 9.7 versus 8.7 months, HR 0.86 [95% CI 0.78-0.95], p=0.002). In multivariate analysis female sex remained associated with longer OS (HR 0.83, 95% CI 0.74 – 0.92, p=0.0005). In subgroup analysis, longer survival was observed in women with adenocarcinoma but not in women with non-adenocarcinoma histology (test of interaction p=0.006, see Figure).There were no differences in any hematological toxicity, or rates of blood or platelet transfusions, between sexes. Women experienced more grade 3 or 4 nausea and vomiting than men (10% versus 5%, p=0.0002). Women experienced more dose delays (39% versus 32%, p=0.02) and dose reductions (32% versus 23%, p