Abstract 4932: Neuro-endocrine negative SCLC is mostly RB1 WT and may be sensitive to CDK4/6 inhibition, especially if CCND1 is amplified

Abstract

Abstract Background: Small cell lung cancer (SCLC) is an aggressive form of lung cancer with limited therapeutic options, a very high mortality rate and is characterized, in most cases, by neuroendocrine features. A small but important subset of SCLC has intact RB1, however, other characteristics of this subset are not well-defined. Here we aim to characterize underlying genomics of SCLC cell lines with functional RB1. Methods: To comprehensively assess the underlying genomics of SCLC cell lines with functional RB1, we examined 52 SCLC cell lines from the Cancer Cell Line Encyclopedia (CCLE) collection. We also integrated CCLE SCLC genomics data with drug sensitivity data from NCI SCLC screen of 420 approved and investigational oncology drugs. Results: Out of 7 neuro-endocrine lineage marker-negative SCLC lines, 6 were RB1 WT. Out of 42 neuro-endocrine lineage marker-positive SCLC cell lines, 3 were RB1 WT. Two RB1 WT SCLC cell lines with CCND1 amplification were sensitive to CDK4/6 inhibitor. Oncogenic alterations in genes such as KRAS, NRAS, SMARCA4, and CDKN2A are rare in SCLC; however, these genes were altered in 7 of 9 RB1 WT SCLC cell lines. Conclusions: Neuro-endocrine lineage marker-negative SCLC are enriched for RB1 WT and may be sensitive to CDK4/6 inhibition especially in context of CCND1 amplification. Neuro-endocrine lineage marker-negative SCLC cell lines are associated with low DLL3 expression. Therefore, RB1 WT SCLC are less likely to respond to DLL3 targeted drugs. However, this may present the opportunity to identify patients with WT RB1 among patients screened for DLL3 ADC clinical trials and having no or very low DLL3 expression. Citation Format: Dmitriy Sonkin, Anish Thomas, Beverly A. Teicher. Neuro-endocrine negative SCLC is mostly RB1 WT and may be sensitive to CDK4/6 inhibition, especially if CCND1 is amplified [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4932.