# Upfront Oxaliplatin–Fluoropyrimidine Chemotherapy and Somatostatin Analogues in Advanced Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Tumors

## TL;DR

Combining oxaliplatin-fluoropyrimidine chemotherapy with somatostatin analogs improves outcomes in advanced GEP-NETs, allowing surgery in some patients.

## Contribution

Demonstrates the effectiveness and safety of upfront combination therapy for advanced GEP-NETs, enabling curative surgery in some cases.

## Key findings

- 25% objective response rate and 87.5% disease control with combination therapy.
- 28.1% of patients experienced tumor shrinkage sufficient for surgery.
- Treatment was well tolerated with mostly mild adverse events.

## Abstract

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often diagnosed at an advanced stage. While somatostatin analogs (SSAs) are the first-line treatment for well-differentiated somatostatin receptor-positive (SSTR+) NETs, they may be insufficient for patients with G2/G3 tumors and high tumor burden. This retrospective study evaluated the efficacy of combining oxaliplatin–fluoropyrimidine chemotherapy with SSA in 32 patients with metastatic G2/G3 GEP-NETs. After a median follow-up of 26 months, the objective response rate (ORR) was 25%, with disease control in 87.5% of cases and tumor shrinkage allowing surgery in 28.1% of patients. Median progression-free survival (PFS) and overall survival (OS) were not reached. The treatment was well tolerated, with mostly mild adverse events. This combination therapy was effective and safe, potentially enabling curative surgery in eligible patients.

(1) Background: GEP-NETs are frequently diagnosed at advanced stage. For well-differentiated somatostatin receptor-positive (SSTR+) NETs, SSA are the preferred first-line therapy. However, in newly diagnosed patients with G2/G3 and a high tumor burden, SSA alone might not be enough; (2) Methods: We conducted a retrospective analysis to assess the effectiveness of combining oxaliplatin–fluoropyrimidine chemotherapy with SSA as an upfront strategy in newly diagnosed metastatic G2/G3 GEP-NET patients treated with oxaliplatin–fluoropyrimidine-based chemotherapy; (3) Results: Between March 2017 and October 2023, 32 pts (19 males, 13 females; M:F = 1.5:1; median age 54 years, range 31–82) were deemed eligible to receive oxaliplatin–fluoropyrimidine chemotherapy in addition to SSA; 14 received XELOX and 18 FOLFOX. After a median follow-up of 26 mo., each patient had completed at least two cycles of chemotherapy. The ORR was 25%, with a median DoR of 21.3 mo. The DCR was 87.5%. Notably, 28.1% of patients experienced tumor shrinkage sufficient for radical surgery on residual tumor lesions, encompassing both primary tumors and metastases; (4) Conclusions: Upfront treatment with the combination of oxaliplatin–fluoropyrimidine and SSA demonstrated effectiveness and safety. This approach may be considered to facilitate conversion surgery in eligible patients.