Second-line oxaliplatin reintroduction or paclitaxel-ramucirumab in metastatic gastroesophageal cancer: a population-based study

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.