(UroToday.com) Erdafitinib is an FDA approved FGFR kinase inhibitor for the treatment of patients with metastatic urothelial carcinoma with pathogenic FGFR3 or FGFR2 mutations who have progressed on prior platinum-based chemotherapy. This approval was based on BLC2001, an open-label phase 2 study which enrolled 99 patients with advanced urothelial carcinoma (UC). In that study, 43% had received at least 2 prior courses of therapy and 79% had visceral metastases. The confirmed objective response was 40% with 3% of patients obtaining a complete response. This abstract provides long-term outcomes from patients in the study.
The study design is shown above. In brief, 212 patients with measurable locally advanced or unresectable/metastatic UC with prespecified FGFR3/2 alterations were enrolled across 14 countries in Asia, Europe, an North America and the optimal treatment schedule was 8 mg daily, with up-titration to 8 mg/day.
A total of 101 patients were in the final 8 mg/d cohort. The median follow-up was 24.0 months and the median treatment duration was 5.4 months. In terms of baseline characteristics, the median age was 67 (36-87) and 88% had progressed or relapsed after chemotherapy. 43% of patients had 2 or more lines of prior therapy and 23% had visceral metastases. 52% of patients had a creatinine clearance <60 ml/min.
The confirmed objective response rate remains 40%. The median duration of response for patients was 6 months and a third of responders had a duration of response greater than 1 year. The median overall survival was 11.3 months with 49 % of patients alive at 12 months and 31% of life at 24 months. There was no significant difference in overall survival by FGFR alteration type or the presence of visceral metastases.
There are no new treatment-related adverse events noted on this study. Of note, central serous retinopathy (CSR) events occurred in 27% of patients which resulted in discontinuation in 3% of patients. Most of the retinopathy events had resolved at the time of data point.
Erdafitinib is an effective therapy for patients with pathogenic FGFR3 or FGFR2 mutations. Clinicians must be aware of the unique treatment-related side effects in this class of medications. Erdafitinib is being combined with checkpoint inhibitors in NORSE; NCT03473743. Given that this therapy is biomarker selected, additional research is ongoing with regards to optimizing liquid biopsy tests for selection. Abstract 3545 (Yablonovitch et al) during this virtual ASCO describes the identification of FGFR2/3 fusions from clinical cfDNA NGS using a de novo fusion caller. Durability remains an issue as almost all patients inevitably progress, even if they initially obtain a CR – combination therapies may be key to delaying progression.
Presented by: Arlene O. Siefker-Radtke, MD, Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute, Twitter: @TheRealJasonZhu, at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.