Efficacy and safety profile of antivascular endothelial growth factor receptor tyrosine kinase inhibitors (avRTKIs) in patients (Pts) with neuroendocrine tumors(NETs): A systematic review and meta-analysis (SRMA).

Abstract

e16216 Background: Vascular endothelial growth factor mediated signaling is central to NETs. As such, multiple avRTKIs have been tested in NETs over the last 2 decades, mostly in small phase II studies. In fact, there have been no randomized phase III trials conducted in United States apart from the one leading to approval of sunitinib in pancreatic (p) NETs. Several other avRTKIs have demonstrated clinical promise including surufatinib in phase III trials conducted in China; this drug is currently under FDA review for potential approval. In the current SRMA, we aim to address this deficiency by benchmarking efficacy and safety profiles of avRTKIs. Methods: A literature search was done to identify all phase II and phase III studies of avRTKIs in pts with NETs published between 1/1/2000–7/31/2021. Data abstraction was performed by one author and validated by another. Efficacy was assessed by aggregating progression-free survival (PFS) and overall response rate (ORR) data. PFS and ORR were assessed using a random effects model separately for pts with pNETs and extra-pancreatic (ep) NETs. Toxicity was assessed by calculating the relative risk (RR) compared to control arm and incidence of adverse events (AEs) of interest. Results: Of 92 identified studies, 17 (with 8 individual avRTKIs) were included in the meta-analysis after excluding redundant studies; baseline study characteristics are listed in the Table.A total of 1611 pts (853 men, 758 women) were available for the analysis; 1194 received avRTKIs. The ORR in pNETs was 18% (95% confidence interval (CI) 13-25%) while the ORR in pts with epNETs was 8% (95% CI 5-12%); test for differences between pNETs and epNETs (x12 = 8.47, p < .01). The median PFS in pNETs was 13.9 months (95% CI 11.43-16.38 months) while median PFS in epNETs was 12.71 months (95% CI 9.37-16.05 months); test for differences between pNETs and epNETs (x12 = .32, p = .57). The incidence (and RR compared to control) of most common ≥ grade 3/4 AEs were hypertension 22.4% (4.48, p < .001), diarrhea 6.4% (RR 3.03, p = .005), neutropenia 5.2% (20.4, p = .036) and proteinuria 4.6% (27.25, p = .001). Incidence (and RR compared to control) of rare but serious complications included non-central nervous system bleeding 8.7% (2.17, p < .001) and cardiac dysfunction 6.4% (2.52, p = .01). Conclusions: Among pts tx with avRTKIs, pts with pNETs demonstrated improved ORR but not PFS compared to these outcomes in pts with epNETs. In addition, this study also benchmarks the incidence and RR of AEs in pts with NETs treated with avRTKIs who are often on therapy longer than other pts.[Table: see text]