Timing of first-line palliative systemic therapy in metastatic esophagogastric adenocarcinoma: A population-based...

With increasing detection of asymptomatic or limited metastatic esophagogastric adenocarcinoma (mEAC), deferring systemic therapy may spare patients toxicity and hospital visits, but its impact on overall survival (OS) and health-related quality of life (HRQoL) is unclear.

Patients diagnosed with mEAC between 2010 and 2023 and treated with first-line systemic therapy were identified from the Netherlands Cancer Registry. Immediate treatment was defined as starting ≤ 8 weeks after diagnosis and deferred as > 8 weeks. We emulated a target trial, restricting to patients with prognostically favourable characteristics eligible for both strategies, to compare OS and HRQoL using inverse probability of treatment weighting to mitigate confounding. An 8-week landmark analysis addressed immortal time bias. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (QLQ-C30) and Esophagogastric 25 (OG25).

Among 7.380 patients, median time to systemic therapy was 29 days (range 0-824 days); 1.162 patients (16%) had a deferred start. 2.812 (35%) patients were eligible for the emulated target trial (494 deferred, 2.318 immediate). No clinically relevant OS difference was observed (median OS from 8 weeks after mEAC diagnosis: 10.9 months (95%CI 9.59-11.86) in the deferred group versus 9.4 months (95%CI 8.90-9.89) in the immediate group; HR 0.91 (95%CI 0.82-1.02)). HRQoL was generally comparable, with some indication of better social and role functioning and less fatigue at 3 months in the deferred start group.

Our findings suggest that deferring could be a reasonable option in selected patients with prognostically favourable characteristics.