Temozolomide in grade III gastroenteropancreatic neuroendocrine neoplasms (G3 GEPNENs): A multicentre retrospective review.

Abstract

BACKGROUND: G3 GEPNENs are often aggressive, and the optimal treatment is unclear for this subgroup of NENs. Temozolomide (TEM)-based regimens have been increasingly used to treat grade 1-2 NENs, but their efficacy in G3 NENs remains undetermined. We aimed to assess the clinical efficacy of TEM-containing regimens in advanced grade 3 GEPNENs.METHODS: A multicentre retrospective review (2008-2018) of patients with metastatic/unresectable G3 GEPNENs who received a TEM-containing regimen was undertaken within a North American partnership to pool data. The primary endpoint was time to treatment failure (TTF). Radiologic response was extracted from local reports.RESULTS: One hundred and thirty patients in six high volume NEN centers were included (median age 55, 64% male, 18% functional, 67% pancreatic NEN). 49% were well-differentiated, 35% poorly-differentiated, and 15% unknown based on local pathology reports. The regimen used was capecitabine and temozolomide (CAP/TEM) in 92% and TEM alone in 8%. Radiological response by local assessment was seen in 36% of patients. Median TTF was 3.6 months and median overall survival (OS) 19.2 months. Six percent of patients required discontinuation of therapy due to adverse events. TTF was longer in first-line treatment (7.8mo vs 2.9mo, HR 1.62, 95% CI 1.11-2.36, p=0.015) and in patients with panNEN compared to GI NEN (5.8 months vs 1.8 months, p=0.04). The overall response rate was higher in the first-line setting (51% vs 29%, p=0.02) and in panNEN (41% vs 23%, p=0.04).CONCLUSION: This is the largest TEM treatment series in G3 NEN, involving collaboration of several major North American NEN centers as a partnership. Thirty-six percent of patients showed some degree of radiographic response, and treatment was generally well-tolerated, although the median duration of response was short. Response rates and time to treatment failure were superior in the first-line setting. CAPTEM should be considered a viable treatment option in this setting. Further randomized trials are warranted.IMPLICATIONS FOR PRACTICE: Neuroendocrine neoplasms (NENs) are heterogeneous and optimal treatment for aggressive Grade 3 (G3) NENs remains undetermined. The CAPTEM regimen (capecitabine and temozolomide) has been used in low-grade pancreas NENs but there are few data for its safety and efficacy in the G3 setting. This manuscript reports on the efficacy of temozolomide-containing regimens, particularly CAPTEM, in management of G3 NENs. The good tolerance and response rate show that CAPTEM should be considered a viable regimen in treatment of G3 NENs pending confirmatory prospective studies.

View details for DOI 10.1002/onco.13923

View details for PubMedID 34342086