Impact of age and sex on chemotherapy (CTx) efficacy, toxicity and survival in early oesophagogastric (OG) cancer: A pooled analysis of 3265 patients from four large randomised trials (OE02, OE05, MAGIC & ST03).

Abstract

4022 Background: No large scale randomised data exists evaluating the impact of age and sex in patients (pts) undergoing potentially curative surgery and CTx for OG cancer. However, differences in age and sex may be contributing factors to variability in CTx dose-response and toxicity which could also impact survival. Methods: Data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival data, hazard ratios were calculated for pts <70 and ≥70 years and between males and females. Pts were allocated to receive neoadjuvant platinum and fluoropyrimidine +/- anthracycline and bevacizumab. Mandard tumour regression grade (TRG) and prevalence of ≥G3 toxicities were compared according to the same subgroups using Chi-squared test. Results: 3265 pts were included for survival analysis (2668 (82%) M, 597 (18%) F; 2626 (80%) <70, 639 (20%) ≥70). A significant improvement in disease specific survival (DSS) (HR 0.78; p<0.001) and OS (HR 0.78; p<0.001) was observed in females vs males. Although OS was worse in older vs younger pts (HR 1.15; p=0.01) no significant difference in DSS was observed (HR 1.04; p=0.52). For those pts who underwent resection following neoadjuvant CTx, older patients (19 vs 13%; p=0.01) and female patients (19% vs 13%, p=0.02) were more likely to achieve more favourable Mandard TRG 1&2 scores. Older pts experienced significantly more ≥G3 neutropaenia (30 vs 22%; p=0.004). Females experienced significantly more ≥G3 nausea (12 vs 7%; p=0.006), vomiting (10 vs 5%; p≤0.001) and diarrhoea (9 vs 4%; p=0.001). Conclusions: This study represents the largest pooled analysis of age and sex differences on safety of neoadjuvant CTx and survival in early OG cancer. Females had significantly improved survival while experiencing more GI toxicities. Older pts achieved comparable DSS and thus, dependent on fitness, should be offered the same treatment paradigm as younger pts.