Pamela L. Kunz, MD, Reviews Results of Temozolomide as Monotherapy or in Combination With Capecitabine in Advanced Pancreatic NETs

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).

Transcript:

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.

References

1. Kunz PL, Graham N, Catalano PJ, et al. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: Final analysis of efficacy and association with MGMT (ECOG-ACRIN E2211). J Clin Oncol. 2022; 40(suppl16):4004. doi:10.1200/JCO.2022.40.16_suppl.4004
2. Kunz PL, Catalano PJ, Nimeiri H, et al. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: A trial of the ECOG-ACRIN Cancer Research Group (E2211). J Clin Oncol. 2018;36(supply 15):4004. Doi:10.1200/JCO.2018.36.15_suppl.4004