Rob Henricus Andreas Verhoeven

Background: Reintroduction of oxaliplatin after first-line treatment might preserve treatment lines and could improve overall survival. Objectives: We investigate whether oxaliplatin reintroduction (OXR) or paclitaxel-ramucirumab (PR) is preferred in terms of overall survival for patients with gastroesophageal adenocarcinoma who have disease progression on first-line treatment. Design: We performed a target trial emulation with a propensity-scored inverse probability weighting approach to resemble a randomized controlled trial. Methods: Observational data was retrieved from the Netherlands Cancer Registry between 2015 and 2018, with a maximum follow-up until 2022. Patients were included if they received a fluoropyrimidine with oxaliplatin in first-line and as subsequent treatment OXR or PR. There was at least 6 months between planned discontinuation of oxaliplatin and disease progression. Results: We included 129 patients in our model and the weighted cohort was well balanced between the two groups. No statistically significant difference in overall survival was observed between treatment groups (HR: 0.76, 95% CI: 0.3–1.5; p = 0.36). Median overall survival was 9.2 months (95% CI: 3.7–25.1) for OXR and 7.9 months (95% CI: 2.8–11.5) for PR ( p = 0.38). Exploratory subgroup analysis did not reach statistical significance. Patients in the OXR-group more often received one or more additional treatment lines, including second-line PR, than patients in the PR group, 47.7% versus 23.3%, respectively. Conclusion: OXR following prolonged response to first-line treatment was associated with similar overall survival compared with PR. In the absence of a demonstrated survival benefit for either treatment, these results propose oxaliplatin reintroduction as a potential option in selected patients.

SummaryInformed consent requirements can introduce significant selection bias. This note evaluates prospective versus retrospective consent models and the utility of propensity score matching to reduce selection bias. While statistical adjustments mitigate the bias, upfront consent frameworks are essential for ensuring unbiased population estimates.