Chemotherapy for Well-Differentiated Pancreatic Neuroendocrine Tumours with a Ki-67 Index ≥10%: Is There a More Effective Antitumour Regimen? A Retrospective Multicentre Study of the French Group of Endocrine Tumours (GTE)

Abstract

Background: The best chemotherapy regimen for well- differentiated pancreatic neuroendocrine tumours (pNETs) with a Ki-67 index ≥10% is still debated. We evaluated the antitumour efficacy of various first-line chemotherapy regimens (streptozocin based, platinum based, or dacarbazine/temozolomide based) in this situation. Methods: In this retrospective multicentre study of the French Group of Endocrine Tumours (GTE), we recruited consecutive patients with advanced well-differentiated pNETs and a Ki-67 index ≥10% receiving chemotherapy between 2000 and 2012. The primary endpoint was progression-free survival (PFS) according to RECIST. Results: Seventy-four patients (42 men, median age 55.5 years) were enrolled from 10 centres. Fifty-one patients (69%) had grade 2 NET and 61 (82%) were stage IV. Median overall survival was 36.3 months. Forty-four patients (59%) received streptozocin-based, 18 (24%) platinum-based, and 12 (16%) dacarbazine/temozolomide-based chemotherapy regimens. These 3 groups were similar regarding age, functioning tumours, grade, the number of metastatic sites, and surgery for primary tumours, but not regarding surgery for metastases and time since diagnosis. Grade 3 NET (HR 2.15, 95% CI: 1.18-3.92, p = 0.012) and age above 55 years (HR 1.84, 95% CI: 1.06-3.18, p = 0.030) were associated with shorter median PFS in the multivariate analyses. Compared to streptozocin-based chemotherapy, no difference was found in terms of PFS for the platinum-based or for the dacarbazine/temozolomide-based chemotherapy regimen: median PFS was 7.2, 7.5, and 7.2 months, respectively (p = 0.51). Conclusions: Patients with intermediate or highly proliferative well-differentiated pNETs may benefit from 1 of the 3 chemotherapy regimens. Increased age and grade 3 were associated with shorter median PFS. Randomised studies searching for response predictors and the best efficacy-tolerance ratio are required to personalise the strategy.

Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When Ki-67 Is ≥10%?

“…In a small series of 18 patients with panNETs treated with sunitinib, the median PFS was 13 and 8 months when the Ki-67 was <10% and ≥10%, respectively [14]. Notably, the efficacy of first-line chemotherapy in panNETs with Ki-67 ≥10% has been specifically investigated in a retrospective multicenter study of the French group of endocrine tumors [15]. Seventy-four patients were enrolled, and a median PFS of 7.2, 7.5, and 7.2 months was recorded for patients receiving streptozocin-, platinum-, or dacarbazine/ temozolomide-based regimens, respectively.…”

Comparison of Temozolomide-Capecitabine to 5-Fluorouracile-Dacarbazine in 247 Patients with Advanced Digestive Neuroendocrine Tumors Using Propensity Score Analyses

“…Roquin et al [44] performed a retrospective comparison of their efficacy in 74 patients with G2 (Ki67 > 10%) pNET depending on the first-line chemotherapy. Although the differences were not statistically significant ( p = 0.37), the ORR were 26, 22 and 50% in patients treated with streptozotocin-, platinum- or DTIC/TEM-based chemotherapies respectively.…”

Oxaliplatin and 5-Fluorouracil in Advanced Well-Differentiated Digestive Neuroendocrine Tumors: A Multicenter National Retrospective Study from the French Group of Endocrine Tumors

“…Streptozotocin-and dacarbazine/temozolomide-based regimens remain historical standard chemotherapy treatment for pancreatic NETs [8][9][10]. More recently, oxaliplatin-based regimens have been introduced giving promising results with a median PFS ranging between 7 and 14 months [11][12][13][14][15][16]. However, these results come from small studies, including a low number of patients and very heterogeneous population involving NETs of different primary tumor sites such as the lung, pancreas, or small bowel, while it is well documented that these tumors have different natural history, biology, and prognosis [1,11,16].…”