1179P Therapeutic sequences in advanced grade 1-2 pancreatic neuroendocriene tumours (pNET)

Abstract

There are several approved treatments in well-differentiated pancreatic neuroendocrine tumors (pNET) but there is no evidence about the best therapeutic sequence for these patients (pts). The objective of this study was to identify the optimal therapeutic sequence. We retrospectively collected data about pts with metastatic or locally advanced well-differentiated grade 1 or 2 pNET treated at 2 neuroendocrine neoplasia (NEN)-dedicated Italian Centers who received at least two lines of treatment for pNET. Radiological progressive disease must have had occurred before switching to the second line of treatment. Factors associated with progression-free survival (PFS) and overall survival (OS), including treatment sequences, were analyzed. Of the 68 included pts, 34 (50%) were male. Fifteen pts (22.1%) had a G1 pNET and 53 (77.9%) a G2 tumor, with median Ki67 of 6.9% (range 0.6-20). Four (5.9%) pts presented localized disease, 55 (80.9%) hepatic lesions, and 9 (13.2%) extrahepatic disease. Primary tumor had been resected in 40 pts (58.8%). First-line therapy was somatostatin analog (SSA) in 52,9%, SSA + peptide receptor radionuclide therapy (SSA+PRRT) in 30.9%, and everolimus (11.8%), chemotherapy (CHT) in 2,9%, and other in 1.5%. Second-line therapy was SSA in 8.8% of pts, high-dose SSA in 7.4%, SSA+PRRT in 9.1%, sunitinib in 11.8%, everolimus in 30.9%, CHT in 16.2%, and other in 5.9%. Median PFS was 14 mo (95%CI 6.9-21.1) for first line and 14.2 mo (95%CI 11.1-17.3) for second line. To evaluate which was the best therapeutic sequence, we compared outcome of 33 pts who received either first-line SSA+PRRT (concomitant) to first-line SSA followed by SSA+PRRT at progression (sequential). In this cohort, median time to strategy failure (TSF) was 46 mo (95%CI 35-56.9) and OS was 94.6 mo (95%CI 61.8-127.6). Median TSF was longer with the sequential than with the concomitant strategy (74.4 vs 40 months, respectively; p=0.007). At multivariate analysis, sequential therapy was associated with a reduced risk for progression (HR 0.28, 95%CI 0.11-0.74, p=0.011). Sequential SSA-PRRT therapy was associated with improved TSF in patients with pNET.