Associate Clinical Professor, University of Connecticut School of Pharmacy, Storrs, CT.
First oral drug for advanced or metastatic bladder cancer.
In April, the FDA approved erdafitinib (Balversa, Janssen). It is the first fibroblast growth factor receptor (FGFR) kinase inhibitor for the second- or later-line treatment of patients with locally advanced or metastatic bladder cancer with FGFR3 or FGFR2 genetic alterations.1 The FDA simultaneously approved a companion diagnostic for use with erdafitinib, the Qiagen therascreen FGFR RGQ reverse transcription (RT) polymerase chain reaction (PCR) kit. FGFR is a family of tyrosine kinases which is activated by genetic alterations found in tumors. It is estimated that up to 3000 patients with bladder cancer have these FGFR genetic alterations.
Approval of erdafitinib was based on the results of a phase 2 multicenter open-label single-arm study that enrolled 87 patients with metastatic or surgically unresectable bladder cancer with FGFR3 mutations or FGFR gene fusions that had progressed on or after at least one prior chemotherapy regimen.2,3 Patients received 8 mg of erdafitinib by mouth daily. The primary outcome measure was an objective response rate (ORR) assessed by a blinded independent review committee.
Enrollment into the trial required patients to also have an Eastern Cooperative Oncology Group performance status score of 0 or 1.4 The results demonstrated a 32.2% ORR (95% confidence interval [CI], 22.4-42%), with a median duration of response of 5.4 months (95% CI, 4.2-6.9). ORR in patients with FGFR3 mutations, FGFR3 gene fusions, and FGFR2 gene fusions were 40.6%, 11.1% and 0%, respectively.2 Responses were observed in patients previously treated with chemotherapy and those who had previously responded to antiprogrammed cell death(PD)-1 or PD ligand-1 therapy.1
The most common adverse reactions included hyperphosphatemia (76%), stomatitis (56%), fatigue (54%), increased serum creatinine (52%), diarrhea (47%), dry mouth (45%), onycholysis (41%), increased alanine aminotransferase (41%), increased alkaline phosphatase (41%), and hyponatremia (40%).1,2 Ocular disorders such as central serous retinopathy or retinal pigment epithelial detachment resulting in visual field defects can occur in up to 25% of patients.2 The median onset is 50 days. This adverse reaction can lead to dose interruptions, reductions, and discontinuations. Additionally, dry eye symptoms can occur in 28% of patients. All patients should receive ocular demulcents as needed, and monthly ophthalmological examinations should be performed during the first 4 months, and every 3 months thereafter. Hyperphosphatemia occurs about 20 days after therapy initiation (range, 8 to 116 days) and may require dose adjustments and/or phosphate binder therapy.
Erdafitinib exhibits drug-drug interactions with medications that are cytochrome P450 (CYP)2C9 and CYP3A4 inhibitors or inducers, serum phosphate level–altering agents, and substrates of OCT2 and P-glycoprotein. Women of childbearing potential and men with female partners of childbearing potential should be advised to use effective contraception while taking and for at least 30 days after discontinuing erdafitinib.
In patients with confirmed FGFR genetic alterations using the FDA-approved companion diagnostic, the recommended dosing for erdafitinib is 8 mg (two 4-mg tablets) daily by mouth with or without food.2 A dose increase to 9 mg (three 3-mg tablets) daily based on serum phosphate levels and tolerability 14 to 21 days after initiation is recommended. If a dose is missed, or vomiting occurs shortly after taking, another dose should not be taken. Patients should resume with the next scheduled dose of the medication. This medication is available in 3-mg, 4-mg, and 5-mg tablets. Average medication cost is not yet available, but this drug will only be available through a single-source specialty pharmacy, US Bioservices.1
1. Janssen. Balversa (erdafitinib) receives U.S. FDA approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma with certain FGFR genetic alterations. Accessed June 18, 2019.
2. Erdafitinib [package insert]. Janssen Pharmaceuticals, Inc; 2019. Accessed June 18,2019.
3. Siefker-Radtke A, et al. First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt). J Clin Oncol. 2918;36(suppl; abstr 4503).
4. ClinicalTrials.Gov. An efficacy and safety study of erdafitinib (JNN-42756493) in participants with urothelial cancer. Accessed June 19, 2019.