5236 - Influence of sex on chemotherapy efficacy and toxicity in oesophagogastric (OG) cancer: a pooled analysis of 4 randomised trials

Background

Sex is a contributing factor to inter-patient variability of chemo metabolism and dose-response, potentially influencing both efficacy and toxicity. Use of a triplet chemo regimen comprising an anthracycline, platinum and fluoropyrimidine remains a standard option in first line treatment of advanced OG cancer. Comparative data on the effect of sex on chemo-related toxicity in this tumour type are lacking.

Methods

Data for pts randomised to ECF, ECX, EOF or EOX chemo within 4 UK-NCRI multicentre RCTs of first line treatment in advanced OG cancer were pooled. Demographic and outcome data, and prevalence of all grade and grade ≥3 toxicity were compared between males and females. Adverse events and response rates were compared by Chi-squared test; survival outcomes by log-rank test.

Results

1654 pts were included; 1328 males (80.3%) and 326 females (19.7%). Age and PS were equally distributed; gastric tumours were more prevalent in females (57.4 vs 34.1%). For toxicities captured commonly across all 4 trials there was no significant difference in all grade or grade ≥3 toxicity between females and males (67.2 vs 62.8%; p=0.19). Females experienced significantly higher rates of nausea and vomiting, both all grade (89.3 vs 78.3%; p<0.001) and grade ≥3 (16.7 vs 9.5%; p<0.001); all grade diarrhoea (53.8 vs 46.9%; p=0.027); all grade stomatitis (49.5 vs 40.7%; p=0.004) and all grade alopecia (81.4 vs 74.3%; p=0.009). There was a trend towards increased rates of grade ≥3 neutropaenia and febrile neutropaenia (45.1 vs 40.4% and 11.8 vs 7.7% respectively), although significance was not reached. Males experienced significantly more all grade peripheral neuropathy (49.3 vs 42.6%; p=0.03). There was no difference in PFS or OS by sex; ORR was higher in males (46.6 vs 40.4%), which approached significance (p=0.051).

Conclusions

This represents the largest pooled analysis of sex effect on outcome and toxicity in advanced OG cancer pts treated with equivalent first line chemo. Females demonstrated significantly higher rates of a number of toxicities, primarily GI in nature, and a trend towards increased rates of neutropaenia. Such results suggest that further research on the impact of sex on the efficacy and toxicity of chemo is necessary.

Clinical trial identification

Editorial Acknowledgement