Sequential Capecitabine/Temozolomide (CAPTEM) and Sunitinib Treatment in Patients with Metastatic Well-differentiated G1/G2 Pancreatic Neuroendocrine Tumors.

Abstract Objective The role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic Pancreatic Neuroendocrine Tumors (PanNET) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced G1/G2 PanNET. Methods In total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group I), and 19 were treated with CAPTEM followed by sunitinib (group II). Results Twenty-three patients were treated with first-line sunitinib or CAPTEM, and twenty were pretreated with somatostatin analog (SSA) or SSA plus transcatheter arterial chemoembolization. The objective response rate (ORR) with first-line treatment was similar in both groups, whereas ORR with second-line treatment was higher in group I than in group II albeit with no significant differences (21.1% vs. 5.3%, P=0.205). Median progression-free survival (PFS) for first-line and second-line treatments did not differ between two groups (11 and 12 months vs. 12 and 8 months, respectively). In subgroup analyses, first-line sunitinib and sunitinib after pretreated SSA had longer mPFS compared to second-line sunitinib after CAPTEM (11 vs. 8 months, P=0.046), whereas first-line CAPTEM and CAPTEM after pretreated SSA had mPFS similar to that of second-line CAPTEM after sunitinib. CAPTEM and sunitinib had similar tolerability. Conclusion Alternating sunitinib and CAPTEM were well-tolerated and associated with similar mPFS in G1/G2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET.