Erdafitinib in Patients with High- and Intermediate-risk Non–muscle-invasive Bladder Cancer: Final Analysis of THOR-2 Study

Background and objective: High-risk (HR) or intermediate-risk (IR) non–muscle-invasive bladder cancer (NMIBC) carries a high probability of recurrence and/or progression. We present the final analysis results of erdafitinib in HR- or IR-NMIBC with fibroblast growth factor receptor 3/2 alterations (FGFR3/2alt) from the phase 2 THOR-2 study. Methods: Cohort 1 (HR-NMIBC papillary only) with prior bacillus Calmette-Guérin was randomized 2:1 to erdafitinib or intravesical chemotherapy. Cohorts 2 (carcinoma in situ ± papillary) and 3 (IR-NMIBC) received erdafitinib. The primary endpoint was recurrence-free survival (RFS) for cohort 1. Exploratory endpoints included complete response (CR) rate and duration of response (DoR) for cohorts 2 and 3. Key findings and limitations: In cohort 1 (n = 73), median RFS was not reached (NR) for erdafitinib (95% confidence interval [CI] 28.6 mo–not estimable [NE]) and 11.6 mo (95% CI 5.3–NE) for intravesical chemotherapy (hazard ratio 0.28 [95% CI 0.13–0.61; nominal p = 0.0007]; median follow-up, 18.5 and 16.6 mo, respectively). In cohort 2 (n = 16), CR rates were 94% (95% CI 70–100%) and 81% (95% CI 54–96%) at 8 and 32 wk, respectively; the median DoR (mDoR) was 23.3 mo (95% CI 10.0–NE; n = 15). In cohort 3 (n = 18), the CR rate was 89% (95% CI 65–99%) and mDoR was NR (95% CI 13.4 mo–NE). Most common treatment-related adverse event in pooled erdafitinib cohorts (N = 83) was hyperphosphatemia (76%). Limitations include early termination in cohort 1 and small sample size that precluded prespecified hypothesis testing. Conclusions and clinical implications: Oral erdafitinib demonstrated high efficacy in FGFR3/2alt HR-/IR-NMIBC, with a manageable safety profile.