The following is a summary of “Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors,” published in the March 2023 issue of Oncology by Kunz, et al.

Advanced pancreatic neuroendocrine tumor (NET) patients have few therapeutic choices that produce quantifiable results. However, according to retrospective and modest prospective trials, capecitabine and temozolomide have been linked to lengthy progression-free survival (PFS) and high response rates (RRs).

Patients with advanced low-grade or intermediate-grade pancreatic NETs were enrolled in the multicenter, randomized, phase II E2211 trial to compare temozolomide and capecitabine/temozolomide. Prior use of temozolomide, dimethyl-triazeno-imidazole-carboxamide or dacarbazine, capecitabine, or fluorouracil was prohibited. Progression within the previous 12 months was another essential eligibility requirement. PFS was the primary outcome, and secondary outcomes included overall survival, RR, security, and methylguanine methyltransferase (MGMT) by immunohistochemistry and promoter methylation.

A total of 144 patients were enrolled between April 2013 and March 2016 to receive either temozolomide (n = 72) or capecitabine with temozolomide (n = 72); 133 eligible patients made up the primary analysis population. The median PFS for temozolomide compared to capecitabine/temozolomide at the scheduled interim analysis in January 2018 was 14.4 months vs. 22.7 months (hazard ratio = 0.58), which was enough to rule out the null hypothesis for the primary endpoint (stratified log-rank P =.022). The median overall survival for temozolomide was 53.8 months in the final analysis (May 2021), whereas it was 58.7 months for capecitabine/temozolomide (hazard ratio = 0.82, P =.42). Response and MGMT deficiency were related.

When temozolomide was used alone instead of in combination with capecitabine, patients with advanced pancreatic NETs experienced a substantial increase in PFS. In randomized research, the median PFS and RR observed with capecitabine/temozolomide are the best ever recorded for pancreatic NETs. Although routine MGMT testing was not advised, it could be considered for specific individuals who required an objective response because MGMT deficit was linked to the response.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.01013