2362MO Erdafitinib (erda) vs chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select FGFR alterations (FGFRalt): Subgroups from the phase III THOR study

FGFRalt are seen in ∼20% of pts with mUC. Erda is an oral pan-FGFR tyrosine kinase inhibitor for pts with locally advanced or mUC with susceptible FGFR3/2alt who have progressed after platinum-containing chemo. THOR (NCT03390504), a randomized phase 3 study, assessed whether erda provided an overall survival (OS) advantage vs chemo in pts with mUC who progressed after 1-2 prior therapies (tx), including anti-PD-(L)1. Pts (≥18 y) with unresectable advanced/mUC and select FGFR3/2alt (mutations/fusions), ECOG PS 0-2, adequate organ function, progression on/after 1-2 prior lines of systemic tx that included anti-PD-(L)1 were randomized 1:1 to erda (8 mg with pharmacodynamically guided uptitration to 9 mg) QD or investigator’s choice of chemo (docetaxel or vinflunine) Q3W until disease progression or intolerable toxicity. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. 266 pts were randomized (median [m] age 67 y, follow-up 16 mo) to erda (N=136) or chemo (N=130). Primary end point was met: mOS 12.1 vs 7.8 mo in erda vs chemo (HR=0.64; 95% CI, 0.47-0.88). OS benefit was seen across subgroups (Table). Erda improved mPFS (6 vs 3 mo) and ORR (46% vs 12%) vs chemo. Most frequent tx-related adverse events (TRAEs): hyperphosphatemia (79%), diarrhea (55%), and stomatitis (46%) with erda; anemia (28%), alopecia (21%), and nausea (20%) with chemo. 46% in each arm had Gr 3/4 TRAEs. 1 and 6 pts had TRAEs leading to death with erda and chemo, respectively.Table: 2362MOSubgroupErda (n=136)Chemo (n=130)HR (95% CI)nmOS, monmOS, moAge<65 y59144590.46 (0.27-0.79)≥65 y77118580.71 (0.47-1.07)Baseline ECOG PS0-11251211990.65 (0.46-0.90)21161130.47 (0.16-1.35)FGFRaltFusion25161980.49 (0.23-1.03)Mutation1081110780.67 (0.47-0.95)Prior lines of tx145143380.61 (0.35-1.09)290129780.67 (0.45-0.98)Visceral metastasisY1031210180.65 (0.45-0.93)N33112990.61 (0.32-1.14)Primary tumorUpper tract41234870.34 (0.18-0.64)Lower tract951182100.82 (0.56-1.18)ChemoDocetaxela1361269110.76 (0.52-1.11)Vinfluninea136124380.60 (0.39-0.92)PD-L1 statusCPS ≥1071011201.98 (0.57-6.91)CPS <1089126890.58 (0.38-0.89)aChemo group tx. Open table in a new tab aChemo group tx. In pts with FGFRalt advanced/mUC after prior anti-PD-(L)1 tx, erda significantly improved OS vs chemo. Clinically relevant subgroups showed a consistent OS benefit for erda. No new safety signals were observed. These results support the role of erda to treat pts with FGFRalt mUC after anti-PD-(L)1 tx.