In a study reported in a research letter in JAMA Oncology, Nimgaonkar et al found that less than half of patients with urothelial cancer who had received first-line platinum-based therapy underwent testing for FGFR alterations and that less than half of patients with susceptible alterations received targeted therapy with the FGFR inhibitor erdafitinib. Among patients who received erdafitinib, overall survival was similar to that observed in clinical trials.
The study used the Flatiron Health database to identify patients with advanced urothelial cancer who received first-line platinum-based chemotherapy and started a later line of therapy between May 2016 and September 2021. The likelihood of initiating erdafitinib compared with standard second-line immunotherapy (atezolizumab, the first approved immune checkpoint inhibitor) in the 6-month interval after each drug’s approval was assessed.
In this study, uptake of the first gene-targeted therapy for urothelial carcinoma was limited despite real-world survival outcomes comparable with clinical trial data…. Further study is required to identify barriers to biomarker testing and erdafitinib use and to explore the potential for blood-based testing to augment identification of susceptible FGFR alterations and improve turnaround times, as seen for other tumors.— Nimgaonkar et al
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Key Findings
Erdafitinib was approved on April 12, 2019. Among 761 patients who received postplatinum therapy from April 1, 2019, to September 1, 2021, 343 (45.1%) underwent FGFR testing, with 71 (20.7%) having a susceptible FGFR alteration. Among the 71 patients, 30 (42.3%) received erdafitinib. Compared with the preapproval period, FGFR testing increased in the postapproval period, but erdafitinib initiation remained at a low level.
Among patients receiving FGFR testing, 305 had tissue-based testing and 74 had blood-based testing, with similar FGFR alteration detection rates (tissue = 19.3%, blood = 18.9%). Among 36 patients who received both tissue- and blood-based testing, alterations were detected in 6. Two of these cases were detected with tissue-based testing, and all six were detected with blood-based testing.
Monthly uptake rates during the first 6 months after approval of both drugs were 0.8% and 3.9% for erdafitinib among all patients and among those with an expected FGFR alteration, respectively, compared with 16.8% for atezolizumab (P < .001 for both comparisons).
Kaplan-Meier survival estimates were similar between real-world and trial patients; median overall survival was 8.97 months (95% CI = 3.93 months–not reached) vs 10.5 months (95% CI = 8.97–14.8 months, P = .15).
The investigators concluded, “In this study, uptake of the first gene-targeted therapy for urothelial carcinoma was limited despite real-world survival outcomes comparable with clinical trial data. Potential reasons include drug toxicity, drug cost limiting access, paucity of data on optimal treatment sequencing, and inadequate FGFR testing. Blood-based testing captured susceptible alterations at a rate similar to that of tissue testing and may identify alterations when tissue-testing does not…. Further study is required to identify barriers to biomarker testing and erdafitinib use and to explore the potential for blood-based testing to augment identification of susceptible FGFR alterations and improve turnaround times, as seen for other tumors.”
Vivek Nimgaonkar, BA, BS, of the Perelman School of Medicine, University of Pennsylvania, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
