Temozolomide in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Retrospective Review

• Published in: The oncologist (Dayton, Ohio) Ohio), 2021-11, Vol.26 (11), p.950-955
• Main Authors: Chan, David L., Bergsland, Emily K., Chan, Jennifer A., Gadgil, Rujuta, Halfdanarson, Thorvardur R., Hornbacker, Kathleen, Kelly, Virginia, Kunz, Pamela L., McGarrah, Patrick W., Raj, Nitya P., Reidy, Diane L., Thawer, Alia, Whitman, Julia, Wu, Linda, Becker, Christoph, Singh, Simron
• Format: Article
• Language: English
• Subjects: Cancer; Capecitabine and temozolomide; Chemotherapy; Dosage and administration; Female; Gastrointestinal Cancer; Humans; Male; Middle Aged; Neoplasms; Neuroendocrine tumors; Outcomes; Patient outcomes; Prospective Studies; Retrospective Studies; Temozolomide; Temozolomide - therapeutic use
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1002/onco.13923

Background Grade 3 gastroenteropancreatic neuroendocrine neoplasms (G3 GEPNENs) are often aggressive, and the optimal treatment is unclear for this subgroup of neuroendocrine neoplasms (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. Materials and Methods A multicenter 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). Forty‐nine percent were well‐differentiated, 35% poorly differentiated, and 15% unknown based on local pathology reports. The regimen used was capecitabine and temozolomide (CAPTEM) 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 (7.8 months vs. 2.9 months; hazard ratio, 1.62; 95% confidence interval, 1.11–2.36; p = .015) and in patients with pancreatic NENs (panNENs) compared with gastrointestinal NENs (5.8 months vs 1.8 months; p = .04). The overall response rate was higher in the first‐line setting (51% vs 29%; p = .02) and in panNEN (41% vs 23%; p = .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 capecitabine and temozolomide (CAPTEM) regimen has been used in low‐grade pancreas NENs but there a