1. The median overall survival was 12.1 months in the erdafitinib group and 7.8 months in the chemotherapy group, with an HR of 0.64.
2. Grade 3 or 4 treatment-related adverse events occurred in 45.9% in the erdafitinib group and 46.4% in the chemotherapy group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Cisplatin-based chemotherapy and immunotherapy are the standard treatment for advanced urothelial cancer, but many patients are ineligible or experience progression. Fibroblast growth factor receptor (FGFR) mutations occur in 20% of cases, and erdafitinib, an FGFR inhibitor, has shown promise. This phase 3 trial investigated erdafitinib versus chemotherapy in advanced urothelial carcinoma patients with FGFR mutations who progressed after immunotherapy. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. Median OS was 12.1 months in the erdafitinib group and 7.8 months in the chemotherapy group, with an HR 0.64 (p=0.005). OS at 6 and 12 months were 85% and 51% in the erdafitinib group vs 66% and 38% in the chemotherapy group. Median PFS was 5.6 months in the erdafitinib group vs 2.7 months in the chemotherapy group, with an HR of 0.58 (p<0.001). ORR was 45.6% in the erdafitinib group vs. 11.5% in the chemotherapy group with a relative benefit of 3.94 (p<0.001). Grade 3 or 4 treatment-related adverse events occurred in 45.9% in the erdafitinib group and 46.4% in the chemotherapy group, with the most common being palmar–plantar erythrodysesthesia syndrome (9.6%), stomatitis (8.1%), onycholysis (5.9%), and hyperphosphatemia (5.2%) in the erdafitinib group and neutropenia (13.4%) and anemia (6.2%) in the chemotherapy group. The strengths of this study include the sample size and methodology, and the limitations include enrolling select mutations. Overall, this study found that erdafitinib resulted in improved outcomes compared to standard chemotherapy among patients with advanced urothelial carcinoma with FGFR mutations after progression on immunotherapy.
Click to read the study in NEJM
Relevant Reading: Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study
In-Depth [randomized controlled trial]: This international phase 3 trial enrolled adults with advanced urothelial cancer and select FGFR3/2 mutations that progressed on previous immunotherapy who were then randomized (1:1) into the erdafitinib group (136 patients) vs chemotherapy group (investigator’s choice of docetaxel or vinflunine, 130 patients). Most patients with PD-L1 results had low PD-L1 expression (CPS <10). The median follow-up time was 15.9 months. Median OS was 12.1 months in the erdafitinib group (95%CI, 10.3-16.4) and 7.8 months in the chemotherapy group (95%CI, 6.5-11.1), with an HR 0.64 (95%CI, 0.47-0.88, p=0.005). OS at 6 and 12 months were 85% (95%CI, 77-90) and 51% (95%CI, 41-60) in the erdafitinib group vs 66% (95%CI, 56-74) and 38% (95%CI, 28-47) in the chemotherapy group. Median PFS was 5.6 months (95%CI, 4.4-5.7) in the erdafitinib group vs 2.7 months (95%CI, 1.8-3.7) in the chemotherapy group, with an HR 0.58 (95%CI, 0.44-0.78, p<0.001). ORR was 45.6% in the erdafitinib group (6.6% CR and 39% PR) vs. 11.5% in the chemotherapy group (0.8% CR and 10.8% PR), with a relative benefit of 3.94 (95%CI, 2.37-6.57, p<0.001). Median DoR was 4.9 months (95%CI, 3.8 to 7.5) in the erdafitinib group vs 5.6 months (95%CI, 2.1-6.0) in the chemotherapy group. Grade 3 or 4 treatment-related adverse events occurred in 45.9% in the erdafitinib group and 46.4% in the chemotherapy group, with the most common being palmar–plantar erythrodysesthesia syndrome (9.6%), stomatitis (8.1%), onycholysis (5.9%), and hyperphosphatemia (5.2%) in the erdafitinib group and neutropenia (13.4%) and anemia (6.2%) in the chemotherapy group. Overall, this study found that erdafitinib resulted in improved outcomes compared to standard chemotherapy among patients with advanced urothelial carcinoma with FGFR mutations after progression on immunotherapy.
Image: PD
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