• Yusuke Kurita, Noritoshi Kobayashi, Kazuo Hara, Nobumasa Mizuno, Takamichi Kuwahara, Nozomi Okuno, Shin Haba, Motohiko Tokuhisa, Sho Hasegawa, Takamitsu Sato, Kunihiro Hosono, Shingo Kato, Takaomi Kessoku, Itaru Endo, Yasuhiro Shimizu, Kensuke Kubota, Atsushi Nakajima, Yasushi Ichikawa, and Yasumasa Niwa.
• Department of Gastroenterology and Hepatology, Yokohama City University, Japan.
• Intern. Med. 2023 Jan 15; 62 (2): 159167159-167.

AbstractObjective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types [hazard ratio (HR), 0.45; p=0.005]. A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p=0.002), grade (G1/G2; HR, 0.42; p=0.006), everolimus treatment line (≤2nd; HR, 0.55; p=0.031), and presence of treatment with metformin (yes; HR, 0.29; p=0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p<0.001), volume of liver metastasis (≤25%; HR, 0.27; p<0.001), everolimus treatment line (≤2nd; HR, 0.27; p<0.001), and presence of primary tumor resection (yes; HR, 0.33; p=0.005). Conclusion The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.

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