Association of sex and age on outcomes of maintenance treatment in patients with advanced esophagogastric adenocarcinoma: an exploratory analysis of the randomized AIO-YMO-0111-MATEO trial

Purpose Sex and age have an impact on efficacy and toxicity of chemotherapy (ctx) in patients (pts) with esophagogastric adenocarcinoma (EGA). However, data are limited, as clinical trials frequently do not report sex-specific differences and older pts are often underrepresented. Methods MATEO is an international randomized trial, confirming non-inferiority of S-1 maintenance therapy compared to continued platinum-based ctx in pts with advanced EGA without disease progression after 3 months of ctx. Toxicity pattern favored S-1 monotherapy. We conducted a post hoc exploratory analysis to assess the impact of sex and age on treatment outcomes. Results In the per-protocol population, 112 pts (72.7%) were male and 42 (27.3%) were female. 37.7% of pts were ≥ ​70 years. Female pts more often had distal stomach tumors (64.3%), while male pts had more esophagogastric junction tumors (76.7%). In a pooled analysis, female pts showed significantly longer progression-free survival (PFS) (median 9.9 vs. 4.3 months, HR 0.56 [95% CI 0.38–0.83], log-rank: p = 0.0033), and overall survival (OS) (median 14.4 vs. 12.2 months, HR 0.65 [95% CI 0.44–0.97], log-rank: p = 0.0348). No age-related differences in PFS and OS were observed between pts ≥ 70 years and < 70 years. In multivariate analyses, female sex, but not younger age, was associated with a trend towards improved OS. No significant sex- or age-specific differences in terms of toxicity were observed. Conclusion Primary tumor location differed by sex. A trend for superior outcome in female pts was observed, whereas age did not have a significant impact on outcome.