Platinum-Based Treatment for Well- and Poorly Differentiated Pancreatic Neuroendocrine Neoplasms

Abstract

Objectives: Pancreatic neuroendocrine neoplasms include well-differentiated tumors (PanNETs) and poorly differentiated carcinomas (PanNECs). Previous reports suggested a role for platinum-based therapy largely in PanNEC. We sought to investigate the role of platinum-based therapy in pancreatic neuroendocrine neoplasms regardless of tumor grade and differentiation.

Methods: Patients with pancreatic neuroendocrine neoplasms treated with platinum-based therapy at Memorial Sloan Kettering (1994-2016) and Verona University Hospital (2008-2016) were retrospectively identified. Response to treatment by RECIST v1.1, overall survival, and progression-free survival were defined. Among patients with available tissue, DAXX, ATRX, Rb, and p53 expression was evaluated to support the histologic grade of differentiation.

Results: Fifty PanNETs, 29 PanNECs, and 22 high-grade tumors with undeterminable differentiation were included. No patients achieved complete response. Overall rate of partial response was 31%, 41% for PanNEC, and 20% for PanNETs. Among PanNETs, partial response was achieved in 33% of G1 (2/6), 10% of G2 (2/19), and 24% of G3 (6/25) tumors. Median overall survival was 29.3 months for PanNETs and 10.9 months for PanNEC (P < 0.001). There was no significant difference in median progression-free survival (P = 0.2).

Conclusions: Platinum-based therapies demonstrated increased activity in PanNEC; however, promising efficacy was also observed in PanNETs, irrespective of grade.

FIGURE 1.

Duration of response according to the differentiation status among patients who achieved partial response with the platinum-based treatment. WD, well-differentiated; PD, poorly differentiated.

FIGURE 2.

Changes in mutational profile in one patient having a grade 2 PanNET during grade progression and after treatment with a somatostatin analog, mTOR pathway inhibitor, and capecitabine/temozolomide. Single nucleotide variations were annotated with gene name and their respective amino acid change with shades of color denoting detected variant allele frequency. Copy number alterations were annotated with gene name and their respective change (amplification or amplification/deletion or deletion). SNV, single nucleotide variations; CAN, copy number alterations; SV, structural variations; DEL, deletion; Abn, abnormal expression; Nl, normal expression.

FIGURE 3.

A, Overall Survival from first platinum treatment by differentiation. B, Progression free survival: calculated from date of first platinum until date of first progression, or date of death, whichever occurred first. WD, well-differentiated; PD, poorly differentiated.