Does Timing of Metastatic Presentation (Synchronous versus Asynchronous) Affect Outcome in Advanced Urothelial Carcinoma?

Lead Investigator: Soumyajit Roy, Rush University Medical Center
Title of Proposal Research: Does Timing of Metastatic Presentation (Synchronous versus Asynchronous) Affect Outcome in Advanced Urothelial Carcinoma?
Vivli Data Request: 9920
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Bladder cancer is the most common cancer in the urinary system with an estimated 549,393 new cases and 199,922 deaths worldwide in 2018. Urothelial carcinoma is the most common histological form of bladder cancer that originates from the inner lining of the urinary bladder and accounts for more than 90% of all cases. Approximately 10% cases present with locally advanced cancers (cancers that has spread beyond the original location but is still confined to near by organs) or metastatic cancers (cancers that has spread to distant organs such as lung, bones) at diagnosis. Prognosis is poor for these patients and less than 15% survive beyond 5 years at diagnosis. While metastatic urothelial carcinoma is considered incurable, advent of immunotherapy (a type of cancer treatment that utilized the body’s natural defenses to target cancer cells) has ushered a new era in the management of these patients.

Timing of metastatic presentation has been shown to be prognostic and predictive of treatment effect in cancers of prostate and kidney. It is usually seen that patients who present with metastatic disease at the time of diagnosis has poor outcome compared to those with metastatic disease at the time of recurrence. However, it is unclear if such correlation exists between timing of metastatic presentation and outcome and treatment response in metastatic urothelial carcinoma. We propose a pooled analysis of 6 clinical trials that investigated the safety and utility of immunotherapy in metastatic urothelial carcinoma. We will collect data about baseline characteristics including timing of metastatic presentation, treatment response, and outcome from individual patients in all the studies. Subsequently we will determine if the outcome of patients with de novo urothelial carcinoma (i.e., those who present with metastatic disease at the time of diagnosis) was significantly different from outcome of patients who presented with recurrent metastatic urothelial carcinoma (who presented with metastatic disease at recurrence). Similarly we will also determine if the outcome with immunotherapy differed among patients with exposure to prior surgery or radiation therapy for urothelial carcinoma compared to those without exposure to prior surgery or radiation therapy.

Requested Studies:

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02951767
Sponsor ID: GO29293 (Cohort 1)

A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
Data Contributor: Roche
Study ID: NCT02302807
Sponsor ID: GO29294

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Data Contributor: Roche
Study ID: NCT02108652
Sponsor ID: GO29293 (Cohort 2)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ramucirumab Plus Docetaxel Versus Placebo Plus Docetaxel in Patients With Locally Advanced or Unresectable or Metastatic Urothelial Carcinoma Who Progressed on or After Platinum-Based Therapy
Data Contributor: Lilly
Study ID: NCT02426125
Sponsor ID: 15679

Real World Evidence of PD-L1, TMB Prevalence and Efficacy of 1st Line Chemotherapy in These High or Low Population for Stage IV Urothelial Cancer
Data Contributor: AstraZeneca
Study ID: NCT04052113
Sponsor ID: D419BR00014

A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination With Platinum-Based Chemotherapy in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma
Data Contributor: Roche
Study ID: NCT02807636
Sponsor ID: WO30070