Purpose: Up to 20% of patients with cholangiocarcinoma (CCA) harbor FGFR gene aberrations. Erdafitinib is approved for pretreated, locally advanced/metastatic urothelial carcinoma with susceptible FGFR3 alterations. The present study evaluated the efficacy and safety of erdafitinib using a pooled analysis of patients with CCA from the RAGNAR and LUC2001 studies. 

Experimental Design: In RAGNAR (phase II, global, tumor-agnostic study) and LUC2001 (an open-label, multicenter, phase IIa study in Asian patients), patients with advanced solid tumors after ≥1 prior lines of therapy received once daily oral erdafitinib (8 mg/day with an option for pharmacodynamically guided up-titration to 9 mg). Patients were pooled for efficacy [objective response rate (ORR) per blinded independent review committee, duration of response (DOR), progression-free survival (PFS), and overall survival (OS)] and safety analyses. 

Results: At a median efficacy follow-up of 14.7 months in 78 erdafitinib-treated patients (RAGNAR: n ¼ 66; LUC2001: n ¼ 12), ORR was 55% [95% confidence interval (CI), 43.4–66.4]. The median time to response was 1.7 months; the median DOR, PFS, and OS were 6.9 (95% CI, 4.37–8.61), 8.5 (95% CI, 6.83– 9.72), and 18.1 (95% CI, 13.40–24.28) months, respectively. The most common treatment-emergent adverse events (TEAE) were hyperphosphatemia (83%), stomatitis (72%), diarrhea (68%), dry mouth (51%), and palmar–plantar erythrodysesthesia (51%); 42% had serious TEAEs, and 12% had TEAEs leading to treatment discontinuation. 

Conclusions: Pooled analyses confirm the robust efficacy of erdafitinib in a diverse population of pretreated patients with advanced/metastatic CCA harboring prespecified FGFR alterations. These findings are consistent with previously observed efficacy of FGFR-targeted agents in patients with CCA.