Fibroblast Growth Factor Receptor Inhibitor-Induced Hyperphosphatemia: A Case Series from a Tertiary Care Center and Literature Review

Background: Fibroblast Growth Factor Receptor Inhibitors (FGFRi) are promising cancer drugs, effective against FGFR2-rearranged cholangiocarcinoma and advanced urothelial carcinoma. Despite their efficacy, they are frequently associated with side effects, notably hyperphosphatemia (hyperP), a significant on-target off-tumor adverse event (AE). Methods: We conducted a search of the electronic health records system at Northwell Health, a large tertiary healthcare system in New York, to identify patients who received treatment with any FGFRi between January 2020 and December 2023. We collected data on the duration of cancer therapy, the incidence and grade of hyperP, time-to-onset of hyperP, and changes in therapy due to hyperP. Additionally, we scrutinized data from landmark clinical trials and the FDA Adverse Event Reporting System (FAERS) database regarding hyperP as an AE associated with FGFRi. Results: In our series, 13 patients were treated with erdafitinib, 2 patients received futibatinib, and 1 patient received pemigatinib. 15 out of the 16 patients (94%) developed hyperP with a median time-to-onset of 12 days with futibatinib, 29 days with erdafitinib, and 90 days with pemigatinib. Most hyperP AEs were grade 2 in patients exposed to erdafitinib. Treatment with phosphate binders was required in all patients on futibatinib and pemigatinib, as well as in 58% of patients on erdafitinib. 4 (33%) of patients treated with erdafitinib required FGFRi dose reduction and 1 (8%) required therapy interruption due to hyperP. Table 1 summarizes the main findings from our cohort, contrasting them with those from large FGFRi randomized clinical trials. Review of the FAERS database showed that hyperP occurred with all FGFRi and constituted 5-15% of all AEs reported with these drugs. Conclusion: Nephrologists should be aware of hyperP as a possible complication of FGFRi therapy. Collaboration with oncologists is essential to maximize treatment benefits and mitigate AEs without therapy interruption.