Patterns and outcomes of current antitumor therapy for high-grade neuroendocrine neoplasms: perspective of a tertiary referral center.

Purpose: Patients with metastatic high-grade neuroendocrine neoplasms (NEN) have an unfavorable prognosis. Treatment patterns and therapy outcome are scarcely evidenced, especially considering the WHO classification updates since 2017, and were thus investigated in this study.

Methods: This retrospective single-center analysis evaluated patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC) treated at the Medical University of Vienna since 2010. The primary endpoints were progression-free survival (PFS) and overall survival (OS) following first-line treatment.

Results: A total of 80 patients were included, 53 (66%) had NEC and 27 (34%) NET G3. Thirty patients had pancreatic NEN (38%), 29 gastrointestinal NEN (36%), 20 an unknown primary (25%), and one gall bladder NEC. All patients had metastatic disease, and all but four received systemic therapy. Platinum/etoposide was the most frequent palliative first-line treatment in NEC (41/47, 87%) and capecitabine/temozolomide (CAPTEM) in NET G3 (14/27, 52%). Overall, the median PFS and OS from first line start were 16.1 and 43.9 months for NET G3 and 6.1 and 12.7 months for NEC, respectively. Median PFS for platin/etoposide in NEC was 6.1 months (overall response rate [ORR] 56%) and for CAPTEM in NET G3 16.9 months (ORR 46%). Irrespective of the limited sample size (n = 4-11), second-line median PFS was short in NEC (FOLFIRI 2.8, FOLFOX 2.6, CAPTEM 5.4, other 2.6 months) and longer in NET G3 (8.2-11.1 months).

Conclusions: The present data from a large European NET center show that multiple treatment strategies are used in NEN and highlight the varying outcomes between NET G3 and NEC.