Siamak Daneshmand, Renata Zaucha, James W.F. Catto, Ben Tran, Viraj A. Master, Y. Lotan, G. Pignot, Andrea Tubaro, Nobuaki Shimizu, Nikhil Vasdev, Eugene K. Lee, Giuseppe Procopio, Fernando Galanternik, Lauren Crow, Kris Deprince, Vahid Naini, Spyros Triantos, Mahadi Baig, Wei Zhu, Jodi K. Maranchie
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.