ISY-12-5 - Current status and perspective of systemic chemotherapies for GEP-NEC

Abstract

According to the World Health Organization grading system for neuroendocrine neoplasms, neuroendocrine carcinoma (NEC) is a poorly differentiated, high-grade malignant tumor, including small and large cell carcinoma. The primary sites of NEC vary, with gastroenteropancreatic NEC (GEP-NEC) accounting for 20%–68% of extra-pulmonary NEC. Treatment guidelines for advanced extra-pulmonary NEC recommend platinum-based chemotherapy regimens, which are suitable for small cell lung carcinoma. There are two large-scale, multicenter retrospective analyses of advanced GEP-NEC: the NORDIC NEC study [Sorbye H et al. Ann Oncol. 2013;24(1)] and the Japanese study [Yamaguchi et al. Cancer Sci. 2014;105(9)]. In both studies, GEP-NEC prognoses varied according to primary organs. Although only etoposide plus cisplatin regimen (EP) was the mainstream first line chemotherapy in NORDIC, EP and irinotecan plus cisplatin regimen (IP) were commonly used in Japan. Both regimens (EP, IP) have been demonstrated to show favorable efficacy and have been acknowledged as de facto standard regimens for advanced NEC, although it remains unclear which of the two regimens might yield more favorable outcomes. Therefore, a phase III study comparing EP and IP in terms of overall survival for patients with recurrent or unresectable GEP-NEC (TOPIC-NEC, UMIN000014795) has been commenced by the Japan Clinical Oncology Group (JCOG). The sample size was set as 140 (70 patients per arm). For second line regimens, amrubicin, irinotecan, and S-1 were commonly utilized in Japan, but no standard regimens have been established. A multicenter phase II study to evaluate the efficacy of everolimus in pancreatic NEC patients who are unresponsive to/intolerant of platinum-based regimens (NECTOR: UMIN000012752) is currently in progress.