Treatment outcomes of patients with G3 neuroendocrine neoplasms.

Abstract

622 Background: Extra-pulmonary neuroendocrine carcinomas (NEC) and neuroendocrine tumors (NET) G3 are aggressive neoplasia that are associated with a limited prognosis. Data on this entity is scarce and optimal treatments are only poorly defined. Methods: 105 patients (♀ = 46; 43.8% and ♂ = 59; 56.2%) with histologically confirmed neuroendocrine carcinoma (NEC; n = 83) or neuroendocrine tumor G3 (NET G3; n = 12) or mixed neuroendocrine non-neuroendocrine neoplasms G3 (MiNEN G3; n = 10) were included into this study. Clinical and pathological characteristics at diagnosis, therapies, outcomes and survival data were recorded. Results: Primary tumor localizations included esophagus/stomach (n = 9; 8.7%), pancreas/duodenum (n = 29; 27.9%), appendix/colon/rectum (n = 25; 24.0%), the genitourinary tract (n = 9; 8.7%) and CUP (n = 32; 30.8%). Median Ki-67 across all patients was 70% (range 25-95) with a statistically significant difference in NEC G3 vs. NET G3 (74%, range 25-95 vs. 33.5%, range 25-69; p < .001). Median overall survival (mOS) was 19.2 (±1.6)months and was significantly higher in NET G3 (38 vs. 16.8 months in NEC; p = .012). First-line therapy in most patients was cisplatin or carboplatin in combination with etoposide (n = 64; 61.0%), followed by FOLFOX (n = 29; 27.6%). Twelve Patients (11.4%) received other chemotherapies. Best overall response to first-line chemotherapy was CR (5.7%), PR (52.4%) SD (17.1%) and PD (21%). In patients with Ki-67 < 55% (n = 40) no significant difference between the different regimens was found. In analyzing median PFS (mPFS) in patients with Ki-67 > 55% (n = 65) the combination of cis- or carboplatin with etoposide (mPFS 6.1±0.5 months) was superior to FOLFOX (mPFS 2.8±1.4 months; p = 0.038). Strikingly, in patients with small-cell NEC (n = 28) the combination of cisplatin/etoposide (mPFS 12.3±3months) showed a superior outcome compared to carboplatin/etoposide (mPFS: 6±1.4months; p = .022). Conclusions: Patients with non resectable NEN G3 should be treated with chemotherapy. In cases with proliferative index > 55% the 1st-line regimen of choice should be platinum in combination with etoposide. The difference in efficacy between carboplatin and cisplatin in our data should be evaluated in a prospective setting.