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Matthew B Schabath,1,2 Tapashi B Dalvi,3 Hongyue A Dai,4 Alan L Crim,4 Anita Midha,5 Norah Shire,3 Nicholas T Gimbrone,1 Jill Walker,6 Danielle M Greenawalt,7 David Lawrence,8 James R Rigas,9 Robert Brody,9 Danielle Potter,9 Naveen S Kumar,4 Shane A Huntsman,4 Jhanelle E Gray2 1Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 3Oncology R&D, AstraZeneca, Gaithersburg, MD, USA; 4M2Gen, Tampa, FL, USA; 5Department of Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, UK; 6Department of Precision Medicine Oncology, AstraZeneca, Cambridge, UK; 7Department of iMED Oncology Informatics, AstraZeneca, Waltham, MA, USA; 8Department of Global Medicines Development, AstraZeneca, Cambridge, UK; 9Department of Global Medical Affairs Oncology, AstraZeneca, Gaithersburg, MD, USACorrespondence: Matthew B SchabathH. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USATel +1 813 745 4150Fax +1 813 745 6525Email matthew.schabath@moffitt.orgPurpose: To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics.Patients and methods: Adult patients with histologically or cytologically documented Stage IIIB/Stage IV/recurrent/progressive NSCLC, Eastern Cooperative Oncology Group performance status 0 to 3, and >2 lines of prior systemic treatment regimens were included in this retrospective analysis. Patients were treated from 1997 to 2015 at H. Lee Moffitt Cancer Center and Research Institute, Tampa, or at 7 community centers across the United States. PD-L1 expression level was determined using the VENTANA PD-L1 (SP263) Assay. EGFR and KRAS mutation status and ALK rearrangements were determined by targeted DNA sequencing; these were obtained from clinical records where targeted DNA sequencing was not performed. TMB was calculated as the total number of somatic mutations per sample.Results: From a total of 136 patients included in the study, 23.5% had tumors with high PD-L1 expression (≥25%). There were no significant differences in patient characteristics, overall survival (OS), and progression-free survival (PFS) between patients with high PD-L1 expression (median OS: 39.5 months; median PFS: 15.8 months) vs low PD-L1 expression (

Endosialin (CD248, TEM-1) is expressed in pericytes, tumor vasculature, tumor fibroblasts, and some tumor cells, including sarcomas, with limited normal tissue expression, and appears to play a key role in tumor-stromal interactions, including angiogenesis. Monoclonal antibodies targeting endosialin have entered clinical trials, including soft tissue sarcomas. We evaluated a cohort of 94 soft tissue sarcoma samples to assess the correlation between gene expression and protein expression by immunohistochemistry for endosialin and PDGFR-β, a reported interacting protein, across available diagnoses. Correlations between the expression of endosialin and 13 other genes of interest were also examined. Within cohorts of soft tissue diagnoses assembled by tissue type (liposarcoma, leiomyosarcoma, undifferentiated sarcoma, and other), endosialin expression was significantly correlated with a better outcome. Endosialin expression was highest in liposarcomas and lowest in leiomyosarcomas. A robust correlation between protein and gene expression data for both endosialin and PDGFR-βwas observed. Endosialin expression positively correlated with PDGFR-βand heparin sulphate proteoglycan 2 and negatively correlated with carbonic anhydrase IX. Endosialin likely interacts with a network of extracellular and hypoxia activated proteins in sarcomas and other tumor types. Since expression does vary across histologic groups, endosialin may represent a selective target in soft tissue sarcomas.

e22167 Background: Ovarian cancer is a histologically and molecularly heterogeneous disease that has a clear need for prognostic and predictive tests to improve treatment and outcomes. The TCC prot...

e15017 Background: Molecular-based pt assessment is commonly used to identify proper candidates for targeted therapies. The objective of our investigation was to examine the utility of the Total Ca...

470 Background: Sunitinib is a standard of care for advanced RCC. Despite efforts to identify predictive molecular markers for patient selection, none are available, likely due to multiple resistance mechanisms. Using the Total Cancer Care (TCC) database, which integrates patient clinical, molecular, and biospecimen data, we devised a tumor genomics and transcriptomics experiment to identify differences between RCC patients who derive prolonged clinical benefit from sunitinib versus those who are resistant. Methods: A discovery set of 34 RCC patients treated with sunitinib at the approved regimen were identified in the TCC database (n=16 treated for ≤6 months, having primarily discontinued for reasons other than tolerability; n=18 treated for ≥18 months). Tumor samples were analyzed by whole exome sequencing (WES) and by parallel 400-gene expression profiling. Following gene mutation identification and supervised gene expression analysis, molecular differences between the two groups were identified and tested for potential association with treatment duration. Results: Of the 34 cases identified, 24 remained for analysis following sample QC failure and clinical review (n=10 and 14 treated for ≤6 and ≥18 months, respectively). Gene expression analysis revealed a 37-gene signature associated with treatment duration: MAPK8 (JNK1) was a leading candidate biomarker (Pearson correlation with log [treatment duration]=–0.70; p=0.06 after Bonferroni multiplicity correction). Pathway-based WES analyses identified 25 potential variants of interest, none remaining statistically significant after correction. However, following genome-wide analysis, a single variant in an intronic region of ING3 was statistically associated with treatment duration (p=0.02). Conclusions: Activation of the PI3K/AKT pathway was a marker of resistance to sunitinib. In contrast, activation of the angiogenic, NOTCH, or JAK-STAT pathways was, to some degree, associated with sensitivity to therapy. However, neither VHL alteration nor lack of expression, nor alteration in chromatin-rearrangement genes, was associated with sunitinib treatment duration. These findings require further validation in a larger and independent cohort.