Patients with advanced pancreatic neuroendocrine tumors (NETs) have few treatment options that yield objective responses. Retrospective and small prospective studies suggest that capecitabine and temozolomide are associated with high response rates (RR) and long progression-free survival (PFS).E2211 was a multicenter, randomized, phase II trial comparing temozolomide vs. capecitabine/temozolomide in patients with advanced low or intermediate grade pancreatic NETs. Key eligibility criteria included: progression within the preceding 12 months and no prior temozolomide, DTIC, capecitabine or 5-fluorouracil. The primary endpoint was PFS; secondary endpoints were overall survival (OS), RR, safety, and MGMT by immunohistochemistry (IHC) and promoter methylation.144 patients were enrolled between 4/2013 to 3/2016 to temozolomide (n = 72) or capecitabine and temozolomide (n = 72); the primary analysis population included 133 eligible patients. At the scheduled interim analysis in 1/2018, median PFS was 14.4 months for temozolomide vs. 22.7 months for capecitabine/temozolomide (HR = 0.58), which was sufficient to reject the null hypothesis for the primary endpoint (stratified log rank p = 0.022). In the final analysis (5/2021), median OS was 53.8 months for temozolomide and 58.7 months for capecitabine/temozolomide (HR = 0.82, p = 0.42). MGMT deficiency was associated with response.The combination of capecitabine/temozolomide was associated with a significant improvement in PFS compared to temozolomide alone in patients with advanced pancreatic NETs. The median PFS and RR observed with capecitabine/temozolomide are the highest reported in a randomized study for pancreatic NETs. MGMT deficiency was associated with response and, although, routine MGMT testing is not recommended, it can be considered for select patients in need of objective response. NCT01824875.
View details for DOI 10.1200/JCO.22.01013
View details for PubMedID 36260828