Table 5.

FDA Benefit-Risk Analysis.

Dimension	Evidence and uncertainties	Conclusions and reasons
Analysis of condition	FGFR2 fusions/rearrangements are present in 10‐20% of patients with iCCA.	iCCA with FGFR2 fusions/rearrangements is a rare, serious, and life threatening disease.
Current treatment options	Treatment options after first-line gemcitabine + cisplatin chemotherapy are limited. No treatment has received regular FDA approval for relapsed CCA. FGFR inhibitors pemigatinib and infigratinib were approved under the accelerated approval pathway and therefore are not considered available therapy.	Patients with CCA with a FGFR2 gene fusion or other rearrangement who have received at least one prior line of treatment have an unmet medical need.
Benefit	The ORR benefit in 103 patients with iCCA enrolled in Study TAS‐120‐101 was 42% (95% confidence interval [CI]: 32, 52) The median DoR was 9.7 months (95% CI: 7.6, 17.1) 43 patients had confirmed PR; 31/43 patients (72%) had a response duration ≥6 months.	There is a meaningful improvement in the magnitude of ORR observed in patients treated with futibatinib in Study TAS‐120‐101 compared to available therapy. The DoR is also clinically meaningful in the context of a disease with estimated survival of 5‐6 months. PMRs have been issued for dose optimization studies.
Risk and risk management	The most common AEs (≥ 30%) were nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, and abdominal pain. The most common laboratory abnormalities (≥ 50%) were increased phosphate, increased creatinine, decreased hemoglobin, and increased glucose. Ocular toxicity (including dry eye, keratitis, and retinal epithelial detachment), and hyperphosphatemia are important risks associated with futibatinib.	A PMR was issued for further characterization of ocular toxicity. Information in the Warnings and Precautions and Dosage and Administration sections of product labeling address these toxicities adequately.

Source: U.S. Food and Drug Administration. NDA Multi-disciplinary Review and Evaluation (NDA 214801) (12).