The FDA has granted an accelerated approval to erdafitinib (Balversa) for the treatment of adult patients with locally advanced or metastatic bladder cancer with an FGFR3
alteration that has progressed on platinum-containing chemotherapy. This is the first targeted therapy approved for metastatic bladder cancer.
The approval is based on the phase II BLC2001 trial, in which erdafitinib induced an overall response rate (ORR) of 32.2% in patients with FGFR2/FGFR3
-positive locally advanced or metastatic bladder cancer. The ORR comprised a complete response rate of 2.3% and a partial response rate of 29.9%. Responders included patients who had been unresponsive to anti–PD-1/PD-L1 treatment.
The FDA noted that a companion diagnostic device approved by the agency should be used in patient selection for erdafitinib. Accordingly, the QIAGEN therascreen®
FGFR RGQ Reverse-transcription (RT)-polymerase chain reaction (PCR) Kit was simultaneously approved as a companion diagnostic for use with erdafitinib.
"I've spent my career specializing in the care of patients with metastatic urothelial carcinoma and understand the need for new treatments for this disease,"
Arlene O. Siefker-Radtke, MD, professor of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, and lead study investigator, said in a statement. "Balversa is an important new therapy for this small subset of patients with urothelial carcinoma who, up until now, had limited treatment options."
The open-label, single-arm, multicenter BLC2001 trial (NCT02365597) included 87 patients with metastatic or surgically unresectable urothelial cancer with FGFR
genomic alterations. As confirmed by a central laboratory, patients had FGFR3
gene mutations (R248C, S249C, G370C, Y373C) or FGFR
gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7). Additionally, all patients had disease progression during or following ≥1 prior chemotherapy regimen.
The median patient age was 67 years (range, 36-87), 74% of patients were white, and 79% were male. Ninety-two percent of patients had an ECOG performance status of 0 or 1 and 66% had visceral metastases.
Regarding prior therapy, 24% of patients had received anti–PD-1/PD-L1 treatment. Almost all (97%) patients had prior cisplatin or carboplatin, including 10% of patients who had been treated with both cisplatin- and carboplatin-based regimens. There were 3 patients who had progressed after receiving platinum-containing neoadjuvant or adjuvant therapy only.
The starting dose of erdafitinib was 8 mg once daily. Patients whose serum phosphate levels were below the target of 5.5 mg/dL between days 14 and 17 had their dose increased to 9 mg once daily. This occurred in 41% of patients. Patients were treated until unacceptable toxicity or disease progression.
The median duration of response was 5.4 months (95% CI, 4.2-6.9). Among 64 patients with an FGFR3
point mutation, the ORR was 40.6% (95% CI, 28.6-52.7) and the ORR was 11.1% (95% CI, 0-25.6) among 18 patients with an FGFR3
fusion. There were no confirmed responses among the 6 patients with an FGFR2
The most common adverse events (AEs) across all grades were phosphate increased (76%), stomatitis (56%), fatigue (54%), creatinine increased (52%), diarrhea (47%), dry mouth (45%), onycholysis (41%), ALT increased (41%), ALP increased (41%), sodium decreased (40%), decreased appetite (38%), albumin decreased (37%), dysgeusia (37%), hemoglobin decreased (35%), dry skin (34%), AST increased (30%), magnesium decreased (30%), dry eye (28%), alopecia (26%), palmar-plantar erythrodysesthesia syndrome (26%), constipation (28%), phosphate decreased (24%), abdominal pain (23%), calcium increased (22%), nausea (21%), and musculoskeletal pain (20%).
Grade ≥3 AEs that were the most common included onycholysis (10%), stomatitis (9%), palmar-plantar erythrodysesthesia syndrome (6%), and paronychia (3%).
“We’re in an era of more personalized or precision medicine, and the ability to target cancer treatment to a patient’s specific genetic mutation or biomarker is becoming the standard, with advances being made in new disease types. Today’s approval represents the first personalized treatment targeting susceptible FGFR
genetic alternations for patients with metastatic bladder cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“FGFRs regulate important biological processes including cell growth and division during development and tissue repair. This drug works by targeting genetic alterations in FGFRs,” added Pazdur.
The accelerated approval of erdafitinib in bladder cancer is contingent on the results of a confirmatory trial.
Balversa (erdafitinib) Prescribing Information. FDA. Accessed April 12, 2019. https://bit.ly/2X67iEm.