FDA Approves Erdafitinib (Balversa), the First Targeted Therapy for Bladder Cancer, Marking Entry into Precision Medicine Era

Author: Handing Haoyiyou

Bladder Cancer (Urothelial Carcinoma) Is the Most Common Urinary Tract Cancer.

In recent years, the advent of immunotherapy has significantly transformed the treatment landscape for bladder cancer. Bladder cancer is currently the malignancy with the highest number of approved PD-1/PD-L1 immune checkpoint inhibitors, among which pembrolizumab (Keytruda) and nivolumab (Opdivo) have become standard-of-care treatments for metastatic bladder cancer.

For previously untreated patients, immunotherapy is currently recommended only for those with high PD-L1 expression. Consequently, a substantial proportion of patients do not benefit from immunotherapy, paving the way for targeted therapy. However, there has been limited progress in the development of targeted therapies for bladder cancer.

Recently, the FDA approved the marketing of Erdafitinib (Balversa) by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, for the treatment of adult patients with locally advanced or metastatic bladder cancer who have FGFR3 or FGFR2 gene alterations and whose disease has progressed despite platinum-based chemotherapy.

Erdafitinib is a once-daily oral pan-FGFR tyrosine kinase inhibitor and the first targeted therapy approved for metastatic bladder cancer.

The FDA stated that an approved companion diagnostic device should be used prior to administering the drug to determine patient eligibility. Accordingly, the QIAGEN therascreen FGFR RGQ RT-PCR Kit was simultaneously approved as a companion diagnostic for Erdafitinib.

Arlene Siefker-Radtke, M.D., Professor of Genitourinary Medical Oncology and Principal Investigator at MD Anderson Cancer Center, stated in a press release: “I have long been dedicated to treating patients with metastatic urothelial carcinoma. However, there has been no significant breakthrough in this disease for a long time. Erdafitinib is an important new therapy that brings new hope to this small subset of urothelial carcinoma patients with limited treatment options.”

Regarding the BLC2001 Clinical Trial

The accelerated approval of erdafitinib was based on the results of the phase II clinical trial BLC2001. In the trial, erdafitinib induced an overall response rate (ORR) of 32.2% in patients with locally advanced or metastatic bladder cancer, including a complete response rate of 2.3% and a partial response rate of 29.9%. Some of these patients had previously been non-responsive to PD-1/PD-L1 therapy.

BLC2001 is an open-label, single-arm, multicenter clinical trial involving 87 patients with metastatic or surgically unresectable urothelial carcinoma harboring FGFR genomic alterations. Central laboratory confirmation verified that patients had FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7). Furthermore, all patients experienced disease progression during or after prior chemotherapy.

The median age of patients was 67 years (range, 36–87); 74% were White, and 79% were male. Ninety-two percent had an ECOG performance status of 0 or 1, and 66% of patients had visceral metastases. Twenty-four percent of patients had previously received PD-1/PD-L1 inhibitors, and nearly all (97%) had been treated with cisplatin or carboplatin, including 10% who had received both cisplatin and carboplatin. Three patients experienced progression after receiving only platinum-based neoadjuvant or adjuvant therapy.

The initial dose of erdafitinib was 8 mg once daily. Between days 14 and 21, the dose was increased to 9 mg once daily in patients (41%) whose serum phosphate levels were below 5.5 mg/dL.

The median duration of response was 5.4 months. The objective response rate (ORR) was 40.6% in 64 patients with FGFR3 gene point mutations and 11.1% in 18 patients with FGFR3 fusions. None of the 6 patients with FGFR2 fusions showed a clear response.

The most common adverse events (AEs) during treatment were hyperphosphatemia (76%), stomatitis (56%), fatigue (54%), elevated creatinine (52%), diarrhea (47%), dry mouth (45%), diabetes insipidus (41%), elevated alanine aminotransferase (41%), decreased appetite (38%), hypoalbuminemia (37%), and dyspnea (37%). Grade 3 or higher adverse events included hyperthyroidism (10%), stomatitis (9%), palmar-plantar erythrodysesthesia syndrome (6%), and paronychia (3%).

“We are in an era of more personalized and precise medicine, where targeted therapies directed at specific gene mutations or biomarkers in patients are becoming the standard of care. This approval represents the first personalized treatment option for patients with metastatic bladder cancer,” said Dr. Richard Pazdur, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research.

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