Efficacy and safety of bevacizumab plus XELOX in patients with unresectable locally advanced or metastatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) are highly vascularized malignancies for which effective treatment options remain limited in the unresectable locally advanced or metastatic setting. Although platinum-based chemotherapy has demonstrated antitumor activity in advanced NETs, evidence supporting its combination with antiangiogenic therapy remains insufficient. In this retrospective study, 85 patients with progressive unresectable locally advanced or metastatic well-differentiated NETs initiated bevacizumab plus XELOX, consisting of bevacizumab at 7.5 mg/kg and oxaliplatin at 130 mg/m² every 3 weeks, together with capecitabine at 1,000 mg/m² twice daily on days 1-14 of each 21-day cycle. Among them, 72 patients who completed at least two treatment cycles and underwent post-baseline radiological evaluations comprised the safety set. The primary endpoint was objective response rate (ORR) by RECIST v1.1, while secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Among the efficacy-evaluable patients, 62 (86.1%) received the regimen as second-line or later systemic therapy. Best responses included complete response (CR) in 1 patient (1.4%), partial response (PR) in 29 (40.3%), stable disease (SD) in 41 (56.9%), and progressive disease (PD) in 1 (1.4%), resulting in an ORR of 41.7% and a DCR of 98.6%. In a conservative sensitivity analysis encompassing all 85 treated patients-treating the 13 non-evaluable patients as non-responders-the ORR was 35.3%. After a median follow-up of 17.2 months, the median PFS was 20.9 months (95% CI, 13.7 months-not reached), with 6-, 12-, and 24-month PFS rates of 84.7%, 69.6%, and 47.3%, respectively. Median OS was not reached, and OS data remained immature. The most frequent any-grade adverse events (AEs) were elevated aspartate aminotransferase (48.6%), anemia (44.4%), lymphopenia and hypoalbuminemia (41.7% each), and hyperglycemia (40.3%), while neutropenia was the most frequent individual grade ≥3 AE (5.6%). No grade ≥3 bevacizumab-specific toxicities were observed. These findings suggest that bevacizumab plus XELOX demonstrates clinically meaningful antitumor activity and a manageable safety profile in advanced NET patients. Given the retrospective and single-arm design, this regimen may represent a potential alternative or sequential treatment option when alkylating-agent-based chemotherapy is unsuitable, whereas prospective comparative studies are warranted to validate these findings and determine its optimal clinical role.