Data from Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non–Small Cell Lung Cancer

作者：Rosalyn Anne Juergens, John M. Wrangle, Frank P. Vendetti, Sara C. Murphy, Ming Zhao, Barbara Coleman, Rosa Sebree, Kristen P. Rodgers, Craig M. Hooker, Noreli C. Franco, Beverly Lee, Salina D. Tsai, Igor Espinoza Delgado, Michelle A. Rudek, Steven A. Belinsky, James Gordon Herman, Stephen B. Baylin, Malcolm V. Brock, Charles M. Rudin · 年份：2023 · DOI：10.1158/2159-8290.c.6545843.v1 · 研究领域：Epigenetics and DNA Methylation、Lung Cancer Research Studies、Lung Cancer Treatments and Mutations

Abstract Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non–small cell lung cancer. This therapy is well tolerated, and objective responses were observed, including a complete response and a partial response in a patient who remains alive and without disease progression approximately 2 years after completing protocol therapy. Median survival in the entire cohort was 6.4 months (95% CI 3.8–9.2), comparing favorably with existing therapeutic options. Demethylation of a set of 4 epigenetically silenced genes known to be associated with lung cancer was detectable in serial blood samples in these patients and was associated with improved progression-free (P = 0.034) and overall survival (P = 0.035). Four of 19 patients had major objective responses to subsequent anticancer therapies given immediately after epigenetic therapy. Significance: This study demonstrates that combined epigenetic therapy with low-dose azacitidine and entinostat results in objective, durable responses in patients with solid tumors and defines a blood-based biomarker that correlates with clinical benefit. Cancer Discovery; 1(7); 598–607. ©2011 AACR. Read the Commentary on this article by Rodríguez-Paredes and Esteller, p. 557 This article is highlighted...