MP56-02 THE EFFECT OF TUMOR MUTATIONAL BURDEN, PDL1 EXPRESSION, AND SOMATIC GENE ALTERATIONS ON ADVANCED BLADDER CANCER RESPONSE TO CISPLATIN CHEMOTHERAPY

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP56-02 THE EFFECT OF TUMOR MUTATIONAL BURDEN, PDL1 EXPRESSION, AND SOMATIC GENE ALTERATIONS ON ADVANCED BLADDER CANCER RESPONSE TO CISPLATIN CHEMOTHERAPY John Heard, Eric Lo, Peris Castaneda, and Michael Ahdoot John HeardJohn Heard More articles by this author , Eric LoEric Lo More articles by this author , Peris CastanedaPeris Castaneda More articles by this author , and Michael AhdootMichael Ahdoot More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cisplatin based chemotherapy is a mainstay of treatment for patients with advanced bladder cancer, however not all patients achieve clinical response. We sought to understand how tumor mutational burden (TMB), PDL1 expression, and somatic tumor alterations were associated with response to cisplatin therapy by utilizing the Tempus Lens platform, a web-based library of clinical and molecular data. METHODS: We selected patients on the Lens platform, managed by Tempus (Chicago, Illinois), with stage 3 and 4 bladder cancer who received cisplatin chemotherapy. Somatic gene mutations via next-generation sequencing (NGS), TMB (>10 mutations/Mb), and PDL1 expression on tumor and immune cells were assessed against rates of clinical response. Analyses were performed with chi-square test at significance of p=0.05. RESULTS: 5.4 million patients were assessed as part of the Lens platform. 4,049 patients with stage 3 or 4 bladder cancer were identified. Clinical response to cisplatin therapy and NGS data was available for 305. In this dataset, PDL1 expression on greater than 10% of tumor cells was associated with worse response to cisplatin therapy as 23% of patients with progressive disease (PD) had this finding compared to 6% of those with complete response (CR) (p=0.046) (Table 1). Similarly, PDL1 expression on great than 10% of tumor infiltrating immune cells was lower in patients with CR compared to PR (0% vs 29%, p=0.02). TMB appeared to be associated with improved response, with high TMP seen in 27% of patients with CR and 19% in patients with PD, although this difference was not significant (p=0.14). Certain somatic alterations were associated with CR while others were associated with PD (Figure 1). CONCLUSIONS: While it is known that PDL1 expression is important in response to immunotherapy, our data suggest PDL1 expression by tumor and immune cells is also associated with response to cisplatin chemotherapy. Specific somatic alterations may be associated with response or lack of response to cisplatin as well. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e773 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Heard More articles by this author Eric Lo More articles by this author Peris Castaneda More articles by this author Michael Ahdoot More articles by this author Expand All Advertisement PDF downloadLoading ...