Role of Targeted Therapies in Management of Metastatic Urothelial Cancer in the Era of Immunotherapy

Author(s):  
Petros Grivas ◽  
Evan Y. Yu
2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5011-5011 ◽  
Author(s):  
Matt D. Galsky ◽  
Romain Banchereau ◽  
Habib Rahman Hamidi ◽  
Ning Leng ◽  
Will Harris ◽  
...  

5011 Background: Tumor mutational burden (TMB), PD-L1 expression, T-effector gene expression (GE) and a fibroblast TGF-β–response signature (F-TBRS) are associated with clinical outcomes with atezo mono in mUC (Mariathasan, Nature, 2018). Here we explore the potential predictive role of these biomarkers and APOBEC mutagenesis in IMvigor130. Methods: Pts receiving first-line (1L) mUC treatment (tx) were randomized 1:1:1 to atezo + PBC, atezo mono, or placebo + PBC. Coprimary efficacy endpoints were PFS and OS. Planned exploratory biomarker analyses included PD-L1 expression, TMB (FoundationOne), and T-effector GE (RNA-seq). Results: The 851 biomarker-evaluable pts (BEP) were representative of the 1200 ITT pts. Biomarker results are shown in Table. PD-L1 IC2/3 was associated with significantly longer OS for atezo mono vs placebo + PBC and a combination of PD-L1 IC2/3, and high TMB (> 10 muts/Mb) identified a pt subset (≈ 14% of BEP) with particularly favorable outcomes with atezo mono vs placebo + PBC; similar results for PD-L1 and TMB were not seen with atezo + PBC vs placebo + PBC. APOBEC mutagenesis was associated with improved OS with atezo-containing regimens whereas high F-TBRS was associated with inferior OS with atezo mono. Conclusions: These results reinforce the potential predictive nature of biomarkers associated with response/resistance to atezo and highlight potentially distinct biology driving benefit with atezo and atezo + PBC. These findings suggest a possible biomarker-directed approach to 1L mUC tx that warrants mechanistic interrogation and prospective validation. Clinical trial information: NCT02807636 . [Table: see text]


2020 ◽  
Vol 203 ◽  
pp. e939
Author(s):  
Florian Roghmann* ◽  
Ralph M Wirtz ◽  
Ademi Santiago-Walker ◽  
Jonas Jarczyk ◽  
Maximilian C Kiregmair ◽  
...  

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 424-424
Author(s):  
Francesco Alessandrino ◽  
Rahul Gujrathi ◽  
Amin Nassar ◽  
Arwa Alzaghal ◽  
Arvind Ravi ◽  
...  

424 Background: Reliable biomarkers to predict response of urothelial cancer to PD-1/PD-L1 inhibitors are still being investigated. Texture analysis represents underlying tumor heterogeneity and may serve as a predictor of response in urothelial cancer. The purpose of this study was to assess predictive ability of CT texture analysis for disease progression in patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitor. Methods: In this IRB-approved HIPAA-compliant retrospective study, from total 93 consecutive patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitors from 2013-2018, 43 patients with measurable disease per RECIST 1.1 criteria who had contrast-enhanced CT performed within three months after starting treatment were included. Progression-free survival was calculated based on serial follow-up CTs, and 11 patients without progression who did not reach 1 year follow-up were excluded. Texture features of measurable lesions on first follow-up CT were extracted (TexRAD Ltd, Feedback Plc, Cambridge, UK). Stepwise logistic regression analysis to identify patients who had progressive disease (PD) at 12 months was performed and performance assessed using receiver operator curves. Results: Of 32 included patients (24 men, 8 women; median age: 65 years) who had total 80 measurable lesions, 22 progressed by 12 months. On first follow-up CT, the entropy and mean of the lesions were higher (p = 0.04, p = 0.02) for patients with PD by 12 months. Calculated specificity and sensitivity of entropy (AUC = 0.79) were 90%, and 63%; of mean (AUC = 0.81) were 90%, and 50%. A predictive model including mean and entropy yielded 95% sensitivity, 80% specificity, 91% PPV, 89% NPV and 91% accuracy (AUC = 0.863) to identify patients with PD at 12 months. Conclusions: Texture analysis of CT performed within three months after starting PD-1/PD-L1 can help predict patients who progress by 12 months with high accuracy. Further studies investigating the correlation of texture analysis with survival endpoints may help validate the role of texture analysis as a biomarker to predict response to PD1/PD-L1 inhibitors.


2013 ◽  
Vol 3 (6-S4) ◽  
pp. 228 ◽  
Author(s):  
Robert S. Svatek ◽  
Arlene Siefker-Radtke ◽  
Colin P. Dinney

Metastatic or unresectable disease is identified in approximately20% of patients presenting with invasive urothelial cancer. Inaddition, up to 50% of patients will develop metastases followingradical cystectomy for clinically localized disease. Multiagentcisplatin-based chemotherapy is considered standard first-linetreatment for these patients. Although urothelial cancer is considereda chemosensitive tumour, metastatic disease is associatedwith poor prognosis and short-term survival. Here, we review therole of a multidisciplinary approach to treating patients with metastaticurothelial cancer.


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