Association between effectiveness of treatment with curative intent and outcomes of first-line systemic therapy in metachronous metastatic gastroesophageal adenocarcinoma

BACKGROUND: Almost half of the patients with gastroesophageal cancer treated with curative intent develop recurrence. It is unknown whether the effectiveness of curative treatment is associated with the outcomes of subsequent first-line systemic therapy.

METHODS: From the Netherlands Cancer Registry, we identified patients with metachronous metastatic gastroesophageal adenocarcinoma(mGEA) initially treated for nonmetastatic disease(2015-2017) with perioperative chemotherapy or neoadjuvant chemoradiotherapy, who later received first-line systemic therapy. Effectiveness of the treatment with curative intent was assessed by time-to-treatment-failure(TTF) and by pathological response. First-line systemic therapy outcomes were assessed by TTF and overall survival(OS). Associations were analysed using Kaplan-Meier curves and multivariable Cox models.

RESULTS: Patients treated with perioperative chemotherapy (n = 81) and neoadjuvant chemoradiotherapy (n = 249) with a TTF longer than the median (19.6 and 14.9 months, respectively) had significantly longer first-line TTF(HR 1.94 95% CI: 1.18-3.19; HR 1.36, 95%CI: 1.04-1.78). This also translated into longer OS for neoadjuvant chemoradiotherapy (HR 1.35 95% CI 1.03-1.77). Pathological response was not associated with systemic therapy outcomes.

CONCLUSIONS: A longer TTF of curative treatment was positively associated with improved first-line systemic therapy outcomes in patients with metachronous mGEA. When counselling patients, TTF of their curative treatment may be considered, whereas pathological response may not.