Efficacy and safety of erdafitinib in patients with advanced or metastatic cholangiocarcinoma and FGFR alterations: Pooled analysis of RAGNAR and LUC2001 studies.
Authors: Pant Shubham , Park Joon Oh , Su Wu-Chou , Schuler Martin H. , Loriot Yohann , Iyer Gopa , Doi Toshihiko , Qin Shukui , Tabernero Josep , Prenen Hans , Folprecht Gunnar , Winter Helen , Zibetti Dal Molin Graziela , Sweiti Hussein , Najmi Saltanat , Hammond Constance , Liao Huimin , Thomas Shibu , Triantos Spyros , Feng Yin-Hsun 
Published: June 2024

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Background: Erdafitinib is an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved in the US for the treatment of adult pts with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 alterations whose disease has progressed on or after ≥1 line of prior systemic therapy. Primary analysis of the RAGNAR study demonstrated tumor agnostic efficacy in patients with solid tumors harboring susceptible FGFR mutations or fusions (1). Results from the LUC2001 study in patients with cholangiocarcinoma were previously presented (2). Here we report on the pooled analysis of patients with cholangiocarcinoma treated in the RAGNAR and LUC2001 studies. Methods: RAGNAR (NCT04083976) and LUC2001 (NCT02699606) enrolled patients with advanced solid tumors after ≥1 prior lines of therapy. RAGNAR patients had exhausted standard of care therapies; LUC2001 enrolled patients only in China, Taiwan, and South Korea. Patients received erdafitinib (8 mg daily, optional up-titration) until disease progression or toxicity. Patients with cholangiocarcinoma and predefined FGFR alterations were pooled into an analysis of efficacy (objective response rate by Independent Review Committee [IRC], duration of response, progression free survival, overall survival) and safety. Results: At data cutoff, 78 patients had received erdafitinib (RAGNAR: 66; LUC2001: 12). Median efficacy follow-up was 15 months. Median (range) age was 56 years (24;77); 60% female, 47% White, 39% Asian. Patients had a median of 2 prior lines of therapy; 92% patients had visceral metastases, and 17% of patients responded to prior therapy. 94% of patients had FGFR2 alterations, and 91% of patients had fusions. Objective response rate by IRC was 55%. Responses were observed in patients with both, fusions or mutations. Median time to onset of response was 1.7 month; median duration of response, progression free survival, and overall survival 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% of patients had serious TEAEs and 12% discontinued treatment due to an AE. No treatment-related deaths were observed. Conclusions: Data from pooled analysis of the RAGNAR and LUC2001 studies confirm robust efficacy of erdafitinib in a diverse population of patients with advanced or metastatic cholangiocarcinoma and prespecified FGFRfusions or mutations. Safety data were consistent with the erdafitinib safety profile. 1. Pant 2023. 2. Feng 2022. Clinical trial information: NCT04083976 and NCT02699606 .