Calcinosis cutis dermatologic toxicity associated with fibroblast growth factor receptor inhibitor for the treatment of Wilms tumor.

Small-molecule inhibitors (nibs) have revolutionized cancer therapy with the emergence of clinically efficacious treatment for advanced-stage malignancies. Fibroblast growth factor receptor (FGFR) inhibitors have shown therapeutic efficacy in malignancies with molecular-genetic alterations in the FGFR/fibroblast growth factor pathway. In a phase 1 clinical trial, erdafitinib, a pan FGFR inhibitor, was well tolerated with a manageable toxicity profile. Hyperphosphatemia was a frequent adverse event in patients treated with erdafitinib; however, no serious complications were observed with this therapy. Here, we report the development of calcinosis cutis dermatologic toxicity in a patient with hyperphosphatemia while treated with a novel selective FGFR inhibitor, INCB 54828-101. Awareness of this form of dermatologic toxicity from an FGFR inhibitor will be important for close monitoring of serum levels of phosphate, FGF23, vitamin D, and calcitriol, the management of adverse serum chemistry with chelators, and treatment decisions to either reduce dose or withhold FGFR inhibitor.

Arudra K ，Patel R ，Tetzlaff MT ，Hymes S ，Subbiah V ，Meric-Bernstam F ，Torres-Cabala C ，Aung PP ，Nagarajan P ，Diab A ，Prieto VG ，Nelson K ，Curry JL ... -  《-》

Metastatic Calcinosis Cutis Secondary to Selective Fibroblast Growth Factor Receptor Inhibitor: Rapid and Complete Regression after Blood Phosphate Normalization and Drug Withdrawal.

Lopez-Castillo D ，March-Rodriguez A ，Rodriguez-Vida A ，Pujol RM ，Segura S ... -  《-》

Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors.

Here, we report results of the first phase I study of erdafitinib, a potent, oral pan-FGFR inhibitor. Patients age ≥18 years with advanced solid tumors for which standard antineoplastic therapy was no longer effective were enrolled (NCT01703481). Parts 2 to 4 employed molecular screening for activating FGFR genomic alterations. In patients with such alterations, two selected doses/schedules identified during part 1 dose-escalation [9 mg once daily and 10 mg intermittently (7 days on/7 days off), as previously published (Tabernero JCO 2015;33:3401-8)] were tested. The study included 187 patients. The most common treatment-related adverse events were hyperphosphatemia (64%), dry mouth (42%), and asthenia (28%), generally grade 1/2 severity. All cases of hyperphosphatemia were grade 1/2 except for 1 grade 3 event. Skin, nail, and eye changes were observed in 43%, 33%, and 28% of patients, respectively (mostly grade 1/2 and reversible after temporary dosing interruption). Urothelial carcinoma and cholangiocarcinoma were most responsive to erdafitinib, with objective response rates (ORR) of 46.2% (12/26) and 27.3% (3/11), respectively, in response-evaluable patients with FGFR mutations or fusions. All patients with urothelial carcinoma and cholangiocarcinoma who responded to erdafitinib carried FGFR mutations or fusions. Median response duration was 5.6 months for urothelial carcinoma and 11.4 months for cholangiocarcinoma. ORRs in other tumor types were <10%. Erdafitinib shows tolerability and preliminary clinical activity in advanced solid tumors with genomic changes in the FGFR pathway, at two different dosing schedules and with particularly encouraging responses in urothelial carcinoma and cholangiocarcinoma.

Bahleda R ，Italiano A ，Hierro C ，Mita A ，Cervantes A ，Chan N ，Awad M ，Calvo E ，Moreno V ，Govindan R ，Spira A ，Gonzalez M ，Zhong B ，Santiago-Walker A ，Poggesi I ，Parekh T ，Xie H ，Infante J ，Tabernero J ... -  《-》

Pan-FGFR inhibition leads to blockade of FGF23 signaling, soft tissue mineralization, and cardiovascular dysfunction.

Yanochko GM ，Vitsky A ，Heyen JR ，Hirakawa B ，Lam JL ，May J ，Nichols T ，Sace F ，Trajkovic D ，Blasi E ... -  《-》

Fibroblast growth factor receptor inhibitors: patent review (2015-2019).

Marseglia G ，Lodola A ，Mor M ，Castelli R ... -  《-》