Everolimus and sunitinib for advanced pancreatic neuroendocrine tumors: a matching-adjusted indirect comparison

BACKGROUND: Everolimus and sunitinib have been approved for the treatment advanced pancreatic neuroendocrine tumors, but have not been compared to each other in a randomized trial and have not demonstrated prolonged overall survival compared to placebo. This study aimed to indirectly compare overall and progression-free among everolimus, sunitinib and placebo across separate randomized trials. METHODS: A matching adjusted indirect comparison was conducted in which individual patient data from the pivotal trial of everolimus (n = 410) were adjusted to match the inclusion criteria and average baseline characteristics reported for the pivotal trial of sunitinib (n = 171). Prior to matching, trial populations differed in baseline performance status and prior treatments. After matching, these and all other available baseline characteristics were balanced between trials. RESULTS: Compared to the placebo arm in the sunitinib trial, everolimus was associated with significantly prolonged overall survival (HR = 0.61, 95% CI = 0.38-0.98, p = 0.042). Compared to sunitinib, everolimus was associated with similar progression-free (hazard ratio for death (HR) = 0.84, 95% CI = 0.46–1.53, p = 0.578) and overall survival (HR = 0.81, 95% CI = 0.49–1.31, p = 0.383). CONCLUSION: After adjusting for observed cross-trial differences, everolimus treatment was associated with longer overall survival than the placebo arm in the sunitinib trial for advanced pancreatic neuroendocrine tumors.