Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03)

Background: There is a lack of large-scale randomised data evaluating the impact of sex and age in patients undergoing chemotherapy followed by potentially curative surgery for oesophagogastric cancer. Patients and methods: Individual patient data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival analysis, hazard ratios (HRs) were calculated for patients aged <70 and >= 70 years, as well as between males and females. Mandard tumour regression grade (TRG) and, >= grade III toxicities were compared using logistic regression models to calculate odds ratios. All analyses were adjusted for the type of chemotherapy received. Results: 3265 patients were included for survival analysis (2668 [82%] male, 597 [18%] female; 2627 (80%) <70 years, 638 (20%) >= 70 years). A significant improvement in overall survival (OS) (HR: 0.78; p < 0.001) and disease-specific survival (DSS) (HR: 0.78; p < 0.001) was observed in females compared with males. No significant differences in OS (HR: 1.11; p = 0.045) or DSS (HR: 1.01; p = 0.821) were observed in older patients compared with younger patients. For patients who underwent resection, older patients (15% vs 10%; p = 0.03) and female patients (14% vs 10%, p = 0.10) were more likely to achieve favourable Mandard TRG scores. Females experienced significantly more >= grade III nausea (10% vs 5%; p <= 0.001), vomiting (10% vs 4%; p <= 0.001) and diarrhoea (9% vs 4%; p <= 0.001) than males. Conclusions: In this large pooled analysis using prospective randomised trial data, females had significantly improved survival while experiencing more gastrointestinal toxicities. Older pa-tients achieved comparable survival to younger patients and thus, dependent on fitness, should be offered the same treatment paradigm. (c) 2020 The Authors. Published by Elsevier Ltd.