Oxaliplatin based chemotherapy for advanced well-differentiated neuroendocrine tumors: A systematic review and meta-analysis

e16240 Background: Currently, chemotherapy is predominantly considered in advanced well-differentiated neuroendocrine tumors (NENs) with high ki67 proliferation index and tumor burden. So far, no standard regimen is available and alkylating agents alone, such as temozolomide or in combination with 5-fluorouracil or capecitabine are widely used. Besides, oxaliplatin based chemotherapy has shown promising antitumor activity without being influenced by the MGMT status. In the current SRMA, we aim to address the efficacy of oxaliplatin based chemotherapy in advanced well differentiated NENs. Methods: We conducted a systematic database search using PubMed/MEDLINE and EMBASE. Eligible studies included randomized and single-arm trials, prospective observational and retrospective studies documenting the clinical efficacy of oxaliplatin based chemotherapy for advanced well-differentiated NENs. The pooled overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were calculated and weighted using generic inverse variance in a random-effects model, as well as subgroup analysis for pts with pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs), G1-2 and G3 NETs. Results: 14 of 24 identified publications were included with a combined total of 865 patients in 3 phase II trial and 11 retrospective studies. 495 pts received FOLFOX, 155 pts XELOX, 130 pts GEMOX and 138 pts plus bevacizumab. 48.4% (419/865) patients were pNETs, and G3 NETs accounted for 21.7% (188/865). The pooled ORR was 27.9% (237/865, 95% CI: 23.2-32.5). pNETs showed much higher ORRs (37.7%,114/303, 95% CI: 31.1-44.3) than epNETs (14.9%, 40/251, 95% CI: 10.5-19.2), χ2 = 32.17, p < 0.001. ORRs in G1-2 NETs was 23.1% (66/273, 95% CI: 18.2-28.1), while in G3 NETs was 45.7% (42/85, 95% CI: 29.7-61.6), χ2 = 19.60, p < 0.001. FOLFOX plus bevacizumab showed a higher ORR (38.3%, 38/98, 95% CI: 28.8-47.9) than the oxaliplatin based regimens without bevacizumab (26.9%, 166/594, 95% CI: 23.4-30.4), χ2 = 4.745, p = 0.029. The median PFS in pNETs was 8.1 months (n = 247, 95% CI: 6.3-9.9), similar to 8.4 months in epNETs (n = 211, 95% CI 5.7-11.2). The median PFS in G1-G2 and G3 NET was 13.4 months (95% CI 9.1-17.6) and 7.1 months (95% CI 4.1-9.6) respectively. Besides, FOLFOX plus bevacizumab also showed a trend of a longer PFS (12.4months, 95% CI 9.5-15.2) than those without bevacizumab (7.6months, 95% CI 6.8-8.3). The pooled median overall survival was 28.8months (95% CI 26.7-30.9). Conclusions: Among the advanced well-differentiated neuroendocrine tumors, oxaliplatin based chemotherapy alone or plus bevacizumab could be a good alternative regimen, especially in pts with pNETs and G3 NETs.