At ASCO 2022, Pamela L. Kunz, MD, spoke about a phase 2 trial investigating temozolomide alone and temozolomide plus capecitabine in advanced pancreatic neuroendocrine tumors.
Pamela L. Kunz, MD, associate professor of Internal Medicine; director of the Center for Gastrointestinal Cancers at Smilow Cancer Center and Yale Cancer Center; chief of Gastrointestinal Medical Oncology; and vice chief of Diversity, Equity, and Inclusion at Yale School of Medicine, spoke with CancerNetwork® at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting about the results of a phase 2 trial (NCT01824875) which analyzed temozolomide (Temodar) as monotherapy or in combination with capecitabine for patients with advanced pancreatic neuroendocrine tumors.1 Results indicated that the combination regimen should be considered a standard of care option in the setting of pancreatic neuroendocrine tumors (pNETs).
There were 144 patients randomized to receive either temozolomide or temozolomide and capecitabine. We presented our initial interim analysis at ASCO 2018 [analyzing] progression-free survival [PFS], which was the primary end point.2 We did meet our primary end point with a median PFS of 22.7 months in the combination arm and 14.4 months in the single-agent temozolomide arm with a hazard ratio of 0.58 [95% CI, 0.36-0.93; P = .022]. That was the final PFS because we met it at the interim analysis. The updated analysis that we presented at this meeting was of overall survival [OS]. We did not reach a statistically significant difference in OS between the arms. This was likely due to a long OS in this patient population of low-grade NETs. The median OS was 53.8 months in the temozolomide arm and 58.7 months in the combination arm [HR, 0.82; 95% CI, 0.51-1.33; P = .42]. There was still a clinically meaningful 5-month difference, but it did not meet statistical significance. This is a real challenge and in the NET clinical trial space, we don’t have agents that typically meet the OS end point. That’s why PFS is a preferred end point for those studies. The temozolomide arm was associated with a 34% response rate and the combination arm [yielded] a 40% response rate. Both were robust response rates. The study was not designed to detect a difference between those 2 arms as that was not the primary end point.