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.
Patients and methods: In RAGNAR (phase 2, global, tumor-agnostic study) and LUC2001 (an open-label, multicenter, phase 2a 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 a blinded independent review committee, duration of response [DOR], progression-free survival [PFS], overall survival [OS]) and safety analyses.
Results: At a median efficacy follow-up of 14.7 months in 78 erdafitinib-treated patients (RAGNAR: n=66; LUC2001: n=12), ORR was 55% (95% CI: 43.4-66.4). Median time to response was 1.7 months; 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. Most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (83%), stomatitis (72%), diarrhea (68%), dry mouth (51%), 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.