Regorafenib plus avelumab in gastroenteropancreatic neuroendocrine neoplasms

The combination of regorafenib plus avelumab showed promising clinical potential in  gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), as shown by a new phase II trial recently published on Nature Cancer.

The new data pertain to the neuroendocrine cohort of the REGOMUNE basket trial, comprising 17 concurrent, single-arm phase 2 trials, each designed to evaluate the efficacy and safety of regorafenib in conjunction with avelumab in distinct tumor types. A total of 47 patients with GEP-NENs were enrolled to receive regorafenib (160 mg per day) and avelumab (10 mg/kg biweekly) in 28-day cycles. The 6-month objective response rate was 18%, with a median progression-free survival of 5.5 months; durable responses of 16.6 months were noted. Treatment-related adverse events were manageable and an exploratory biomarker analysis identified PD1 and indoleamine 2,3-dioxygenase 1 expression and activity as potential resistance markers. As authors say, «Although the response rate observed in our cohort aligns with those previously reported for multikinase inhibitors, which ranged from 9% to 16%, it is noteworthy that objective responses were observed in participants who were previously exposed to such treatments. This detail suggests that the synergistic effect of antiangiogenic agents and PD1/PD-L1 inhibitors may offer a strategy to overcome secondary resistance to tyrosine kinase inhibitors in at least a subset of persons with GEP-NENs. Our preliminary findings indicate that the combination of regorafenib and avelumab merits further investigation for the management of persons suffering from GEP-NENs. Furthermore, the predictive biomarkers we identified require additional validation in future studies to confirm their utility», authors conclude.