Dr. Siefker-Radtke notes that there have been decades of chemotherapy for the treatment of metastatic urothelial cancer, and even early “immunotherapy”. These include cisplatin, CisCA, M-VeCarbo, FAP (5-FU, IFNa, cisplatin), gem/cis, taxol/carboplatin, escalated M-VAC, dose-dense MVAC, and taxotere + cisplatin. Gemcitabine-cisplatin is the ‘standard’ chemotherapy for metastatic bladder cancer treatment, leading to a median OS of 13 months, although it is associated with more myelosuppression as compared to MVAC.
The current standards, according to Dr. Siefker-Radtke, for urothelial cancer are as follows:
- Cisplatin-based chemotherapy remains the standard in the management of bladder cancer
- In the neoadjuvant space, MVAC is still the best by prospective data, however, gemcitabine-cisplatin is used based upon metastatic data extrapolation
- In the metastatic/incurable space, cisplatin eligible patients receive gemcitabine-cisplatin, and for cisplatin-ineligible patients, patients receive pembrolizumab or atezolizumab
- In the second line (after progression on cisplatin-based chemotherapy), there are five immunotherapy agents approved for bladder cancer: pembrolizumab, atezolizumab, nivolumab, durvalumab, and avelumab
- 2 weeks of MVAC, or
- Gemcitabine-cisplatin on a 3-week schedule
- Improved toxicity profile
- Modest clinical benefit
- Similar efficacy compared to traditional chemotherapy, with slightly improved response rates and slightly increased long-term survival
- Improvement in toxicity
- Shorter time on treatment
- Basal – highest proliferation, with the worst clinical outcomes; however, the highest likelihood to benefit from neoadjuvant chemotherapy
- Luminal – intermediate proliferation, often associated with FGFR3 mutations
- p53-like – lowest proliferation, and associated with stromal markers
Dr. Siefker-Radtke concluded with an excellent final slide summarizing the paradigm shift in urothelial cancer, and once again highlighting that urothelial cancer is no longer one disease entity:
1. Sternberg CN, de Mulder PH, Schornagel JH et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol 2001;19:2638-2646.
2. McConkey DJ, Choi W, Shen Y, et al. A prognostic gene expression signature in molecular classification of chemotherapy-naïve urothelial cancer is predictive of clinical outcomes from neoadjuvant chemotherapy: A phase 2 trial of dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in urothelial cancer. Eur Urol 2016;69(5):855-862.
Presented by: Arlene Siefker-Radke, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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