Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with intermediate-risk non–muscle-invasive bladder cancer (IR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 3 interim analysis.
Authors: Daneshmand Siamak , Zaucha Renata , Gartrell Benjamin Adam , Lotan Yair , Hussain Syed A. , Lee Eugene K. , Procopio Giuseppe , Galanternik Fernando , Naini Vahid , Carcione Jenna , Triantos Spyros , Baig Mahadi , Maranchie Jodi K. 
Published: March 2023

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Background: Current treatments (tx) of papillary NMIBC are not selective. Novel tx can be assessed on measurable disease (eg, a marker lesion) to rapidly and directly assess antitumor efficacy. FGFR inhibitor therapy may improve outcomes for pts with IR-NMIBC with FGFR3/2alt. Erdafitinib (erda) is an oral selective pan-FGFR tyrosine kinase inhibitor approved for locally advanced or metastatic urothelial cancer in adults with FGFR3/2alt who have progressed during or following ≥1 line of platinum-containing chemotherapy. THOR-2 (NCT04172675) is a multicohort phase 2 study of erda in pts with NMIBC. We report results in an exploratory cohort of pts with IR-NMIBC with FGFRalt (Cohort 3). Methods: Inclusion: age ≥18 y, with histologically confirmed NMIBC with FGFR3/2alt (local/central testing) and recurrent IR disease, with all previous tumors being low grade (Gr) (Gr 1-2), Ta/T1, no previous carcinoma in situ, risk of progression <5% in the next 2 y, and risk of recurrence >50%. All tumors were removed by transurethral resection of bladder tumor except for a marker lesion (single untouched 5-10 mm lesion). Pts received continuous oral erda 6 mg once daily without uptitration in 28-d cycles. Urine cytology was performed at the time of complete response (CR). Pts with a partial response (PR) or CR ≤3 mos of starting erda continued erda for up to a maximum of 2 y, until progressive disease, intolerable toxicity, withdrawal of consent, investigator decision to discontinue tx, or study closure. Primary exploratory end point: CR rate (CR = disappearance of the marker lesion without any new lesions; if there is a remnant of the marker lesion, no viable tumor should be seen on histopathological examination); key secondary end point: safety. Results: As of the data cutoff (Sep 2022) (median follow-up of 6.2 mos), 10/11 enrolled pts have received erda (enrolled population; median age: 66 y [range 47-77]; 9 Ta, 2 not staged). Pts received erda for a median duration of 2.9 mos (range 1.1-8.4). Efficacy (n=8 evaluable): 6 pts had CR (CR rate, 75.0%; 95% CI, 34.9-96.8%), and 1 had PR. Of 7 pts with CR or PR, median observed duration of response was 2.8 mos. Safety (≥1 dose of erda; n=10): the most common tx-emergent adverse events (TEAEs) were hyperphosphatemia (90.0%; n=9), diarrhea (60.0%; n=6), dry mouth (50.0%; n=5), dry skin (30.0%; n=3), dysgeusia (30.0%; n=3), and constipation (30.0%; n=3). One pt had Gr ≥3 dysuria (10.0%) and 1 (10.0%) had Gr ≥3 tx-related diarrhea. One pt (10.0%) had Gr 1 tx-related central serous chorioretinopathy. No pts had tx-related serious TEAEs or tx-related TEAEs leading to discontinuation. No deaths occurred. Conclusions: Data from Cohort 3 of THOR-2 demonstrate efficacy in adult pts with IR-NMIBC with FGFRalt. Safety data were consistent with the known safety profile of erda. Clinical trial information: NCT04172675 .