A Brief Report of a Phase II trial Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer.

•Epigenetic modifications including DNA methylation have been implicated in platinum resistance in small cell lung cancer tumors and cell lines. This Phase II study investigated the combination of hypomethylating agent guadecitabine in combination with carboplatin in relapsed extensive stage small cell lung cancer.•The addition of guadecitabine to carboplatin did not lead to meaningful improvement in survival of patients with relapsed extensive stage SCLC and was associated with considerable toxicity. The lack of benefit may have been mediated in part by alternate epigenetic modifications of chemo resistance in SCLC such as histone modifications.•Additional characterization of molecular subtypes and transcriptional modifications of SCLC with new tools such as cell free DNA are needed to develop new therapeutic approaches to relapsed extensive SCLC.