Efficacy of <scp>FOLFIRINOX</scp> in digestive neuroendocrine carcinoma

Digestive neuroendocrine carcinomas (NEC) are rare, aggressive, and treatment-resistant malignancies. Platinum and etoposide are recommended as first line treatment; however, with limited benefit in colorectal NEC and in NEC with low Ki67 of 20%-55%. There is no firm evidence for second-line treatment. Being efficient in digestive adenocarcinomas, FOLFIRINOX is sometimes used also in patients with NEC. In this retrospective cohort study, patients with digestive NEC who received FOLFIRINOX and were diagnosed 2014-2021 were retrospectively identified at three Scandinavian centers. Histology was re-evaluated according to the 2019 WHO classification to exclude NET G3 tumors. Patient characteristics, treatment response, and survival outcomes were assessed. Fifty cases were identified; four of these were classified as mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN). The most common primary sites were colon (n = 17) and pancreas (n = 13). FOLFIRINOX was administrated predominantly in later lines (82%). Overall response rate (RR) was 44% (95% confidence interval (CI): 29%-58%) and disease control rate 72% (CI: 57%-83%), while median progression free survival was 5.6 months (CI: 4.3-6.9 months). Twenty-three patients with colorectal primary, 12 patients with Ki67 < 55%, and 33 patients previously exposed to platinum and etoposide as first line; the RR was 52%, 50%, and 39%, respectively. This study suggests a role for FOLFIRINOX in digestive NEC. High efficacy was observed, even in patients with hard-to-treat colorectal primaries, in those with Ki67 < 55%, and in patients previously exposed to platinum and etoposide.