Timing of first-line palliative systemic therapy in metastatic esophagogastric adenocarcinoma: A population-based analysis & target trial emulation.

Background

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.

Methods

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).

Results

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.

Conclusions

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