ASCO 2018: SPEAR-Bladder (Study Informing Treatment Pathway Decision in Bladder Cancer): First-Through Third-Line Time to Treatment Failure in the US

Chicago, IL (UroToday.com) Over the last three years, there have been exciting developments for immunotherapy for patients with advanced and metastatic urothelial carcinoma, stemming from several phase II and phase III trials [1-7]. This has resulted in FDA approval for several immunotherapy agents, including pembrolizumab, avelumab, durvalumab, atezolizumab, and nivolumab, in the second line and cisplatin ineligible first-line setting. Gurjyot K. Doshi, MD, and colleagues presented results of their analysis assessing time to treatment failure among patients with metastatic urothelial carcinoma treated with systemic chemotherapy and immunotherapy regimens in the US community oncology setting.

For this study, the authors utilized a retrospective assessment of patients with metastatic urothelial cancer receiving treatment from January 2015 to April 2017 using the US Oncology Network (USON) electronic health records database, iKnowMed (iKM), and the US Social Security Death Index databases. USON includes over 400 outpatient oncology clinics in the United States, and the iKM database captures information pertaining to clinical care, including diagnosis, laboratory tests, therapy administration, line of therapy, staging comorbidities, and ECOG performance status. Time to treatment failure (TTF) was defined as the interval between treatment initiation in the first, second, or third line and discontinuation for any reason. Time to treatment failure was compared between the chemotherapy and immunotherapy cohorts using Kaplan-Meier and Cox proportional hazard modeling.

There were 430 patients who initiated first-line treatment, with a median age 72 years of which the majority were male (78.4%). There were 218 patients initiating second-line treatment with a median age of 69 years, of which 76.1% were male. Finally, there were 45 patients initiating third-line treatment with a median age of 67 years, of which 73.3% were male. Among patients receiving first-line platinum-based combinations, 26.5% were treated with carboplatin/gemcitabine, 18.4% with cisplatin/gemcitabine, and 9.3% with carboplatin/paclitaxel. Immunotherapy regimens were received by 57.8% of patients in second line and 64.4% in the third line setting. Interestingly, patients treated with immunotherapy regimens in all settings (first, second and third line) had a significantly longer TTF than those treated with systemic chemotherapies: 

SPEAR immunotherapy chemotherapy

Patients enrolled in treatment intervention clinical trials are typically the “best of the best” (excellent performance status, etc). Studies such as the results presented herein are important to understand the dissemination, treatment patterns and outcomes in the real-world, community setting. Although a possible limitation of this study was the heterogeneous chemotherapy regimens utilized and small sample sizes, patients in the immunotherapy cohort stayed on therapy for longer periods than chemotherapy-treated patients. Future research should focus on exploring underlying factors that influence treatment choice, reasons for treatment discontinuation, and the associated impact on clinical outcomes. 

References:
1. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376(11):1015-1026. 
2. Sharma P, Callahan MK, Bono P, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): A multicentre, open-label, two-stage, multi-arm, phase I/II trial. Lancet Oncol 2016;17(11):1590-1598.
3. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18(3):312-322.
4. Balar AV, Castellano D, O’Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): A multicentre, single-arm, phase 2 study. Lancet Oncol 2017;18(11):1483-1492.
5. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 2016;387(10031):1909-1920.
6. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, phase 2 trial. Lancet 2017;389(10064):67-76. 
7. Powles T, Duran I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomized controlled trial. Lancet 2018;391:748-757.

Presented by: Gurjyot K. Doshi, US Oncology Network, McKesson Specialty Health, Houston, TX

Co-Authors: Abhijeet Bhanegaonkar, Murtuza Bharmal, Hemant Phatak, Marley Boyd, Kathleen M Aguilar, Mairead Kearney; US Oncology Network, McKesson Specialty Health, Houston, TX; EMD Serono Inc., Rockland, MA; Merck KGaA, Darmstadt, Germany; EMD Serono, Rockland, MA


Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
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