Yu’s opinion and thoughts regarding the future of ramucirumab for urothelial carcinoma is:
- The press release for overall survival stated a strong trend but was not statistically significant. He expects these results to be presented at ESMO 2018
- Will regulatory approval be achieved given the overall survival findings?
- If regulatory approval is achieved, where should it be positioned in the treated pathway? Immediately after combination platinum-based chemotherapy or after PD-1/PD-L1 antibody therapy?
Arlene O. Siefker-Radtke, MD, presented results of the erdafitinib BLC2001 phase II trial earlier this meeting. Erdafitinib is an FGFR inhibitor with activity in patients with metastatic urothelial carcinoma and FGFR alterations, a pan-FGFR inhibitor targeting all 4 receptor subtypes. As part of this phase II study, 99 patients have treated with a median 5 cycles of optimized erdafitinib dose regimen. Of these, 12% were chemo naïve, 43% had received ≥ 2 prior lines of therapy, 79% had visceral metastases. There was a 40.4% confirmed ORR by RECIST 1.1 criteria (3% CR, 37.4% PR) and 79.8% disease control rate (CR + PR + SD). In general, responses were early, within first 1-2 months. In terms of PFS and OS:
- PFS: Median PFS 5.5 months
- OS: Median OS 13.8 months
Yu’s opinion and thoughts regarding the future of FGFR inhibitors for urothelial carcinoma is
- What is the best predictive/companion biomarker? An assay or fusions vs mutations vs amplifications?
- Should this eventually go first-line for those who harbor FGFR alterations?
- Should we be using pan-kinase inhibitors or specific monoclonal antibodies? And which FGFR is most important to target?
- How much will toxicity matter?
- Enfortumab vedotin ADC that targets Nectin-4 à tested in the phase I setting, with ongoing phase II trials, and a planned phase III trial vs investigators choice of chemotherapy among patients progressing after PD-1/PD-L1 therapy
- AGS15e ADC that targets SLITRK6
- Sacituzumab Govitecan (MMU-132) ADC that targets TROP-2
- Multiple new therapeutic options have the potential for regulatory approval with varying mechanisms of action
- Anti-angiogenic, FGFR pan-kinase and monoclonal antibodies, antibody drug conjugates, and PARP inhibitors are all being explored
- There is hope for molecular stratification of treatment for urothelial carcinoma in the near future
- Petrylak DP, Chi KN, Drakaki A, et al. RANGE: A randomized, double-blind, placebo-controlled phase 3 study of docetaxel with or without ramucirumab in platinum refractory advanced or metastatic urothelial carcinoma. ESMO 2017, abstr LBA4.
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
Read More: The 2018 ASCO Presentation: A Subgroup Analysis of the East Asia Population in RANGE