BACKGROUND

• Certain FGFR genetic alterations have been identified as predictive biomarkers of response to erdafitinib.¹
• BALVERSA^® (erdafitinib) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least 1 line of prior systemic therapy.²
  • Select patients for the treatment of locally advanced or mUC with BALVERSA based on the presence of susceptible FGFR genetic alterations in tumor specimens as detected by a United States Food and Drug Administration (FDA)-approved companion diagnostic for BALVERSA.
  • Limitations of Use: BALVERSA is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy.
  • Information on FDA-approved tests for the detection of FGFR3 genetic alterations in urothelial carcinoma (UC) is available at: http://www.fda.gov/Companion Diagnostics.
• During the BLC2001 study (NCT02365597), a clinical trial assay performed at a central laboratory was used to identify patients with locally advanced or mUC that had at least 1 of the following genetic alterations: FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7).²
• The FDA-approved molecular diagnostic test (ie, CDx) commercially available from QIAGEN identifies patients with four point mutations and two fusions in the FGFR3 gene who may be eligible for treatment with BALVERSA.³
• A study of the analytical concordance of 3 independent diagnostic assays, including the QIAGEN therascreen^® reverse transcriptase-polymerase chain reaction (RT-PCR) RGQ (Rotor-Gene Q) assay, for the detection of FGFR alterations in solid tumor tissue (muscle invasive bladder cancer [MIBC; n=18], non-muscle invasive bladder cancer [NMIBC; n=23], cholangiocarcinoma [CCA; n=12], and non-small cell lung cancer [NSCLC; n=1]) was conducted. Detection of FGFR3/2 alterations were similar with Thermo Fisher and Illumina next generation sequencing (NGS) platforms compared to the QIAGEN RT-PCR assay. Analyses showed high concordance between the QIAGEN and NGS assays with 100% concordance in positive, negative, and overall agreements.⁴
• Please refer to national treatment guidelines for recommendations regarding optimal timing of genomic testing for patients with locally advanced or before mUC.

PRODUCT LABELING

Please refer to the following sections of the Full Prescribing Information which are relevant to your inquiry: INDICATIONS AND USAGE, DOSAGE AND ADMINISTRATION, and CLINICAL STUDIES.

QIAGEN therascreen^® FGFR RGQ RT-PCR Kit

Johnson & Johnson is not the owner or manufacturer of the kit, but we can share the following information provided by QIAGEN.

The therascreen^® FGFR RGQ RT-PCR kit is a real-time RT-PCR test for the qualitative detection of 2 point mutations in exon 7 [p.R248C (c.742C>T), p.S249C (c.746C>G)], 2 point mutations in exon 10 [p.G370C (c.1108G>T) and p.Y373C (c.1118A>G)] and 2 fusions (FGFR3-TACC3v1 and FGFR3-TACC3v3) in the FGFR3 gene in ribonucleic acid (RNA) samples derived from formalin-fixed paraffin-embedded (FFPE) urothelial tumor tissue.  The test is indicated for use as an aid in identifying patients with cases of UC which harbor these alterations are therefore eligible for treatment with BALVERSA.³

Specimens are processed using the RNeasy DSP FFPE kit for manual sample preparation followed by reverse transcription and then automated amplification and detection on the RGQ MDx (US) instrument.³

A bridging study was conducted to determine the clinical concordance between the clinical trial assay used during BLC2001 and the therascreen^® FGFR RGQ RT-PCR kit.³ The FDA determined the therascreen^® FGFR RGQ RT-PCR kit to be concordant with the clinical trial assay, as reflected by the approval of the test as a companion diagnostic for use with BALVERSA.⁵

• For additional information regarding the therascreen^® FGFR RGQ RT-PCR kit, please consider the following options:
  • Visit the QIAGEN website at: https://www.qiagen.com/us/knowledge-and-support/resources for information about the test, plus a link to download the kit handbook as a pdf file. The kit handbook contains the Indications for Use Statement, background information on the technology utilized in the test assays, and technical and clinical performance data.
  • Contact QIAGEN North American technical services at [email protected] or 800-362-7737.
• To locate laboratories that can conduct the therascreen^® FGFR RGQ RT-PCR test, please contact QIAGEN North American technical services at [email protected] or 800-362-7737.

additional information

• Analytical concordance of 3 independent diagnostic assays for the detection of FGFR alterations in solid tumor tissue (MIBC [n=18], NMIBC [n=23], CCA [n=12], and NSCLC [n=1]) was evaluated to potentially identify molecular targets for tailored treatment and patients for clinical trial eligibility. Detection of FGFR3 and FGFR2 alterations were similar with Thermo Fisher and Illumina NGS platforms compared to the QIAGEN therascreen^® RGQ RT-PCR assay. Analyses showed high concordance between the QIAGEN and the NGS assays with 100% concordance in positive, negative, and overall agreements as summarized in the Table: Accuracy of NGS and RT-PCR Assays below.⁴
  • Of 54 samples tested with the QIAGEN assay, 51 met quality control metrics with the Thermo Fisher assay and 47 with the Illumina assay. The QIAGEN assay identified 15 FGFR3 mutations and 2 FGFR fusions in 17 patient samples with 1 patient sample having a dual S239C mutation and FGFR3:TACCv1 fusion. Both NGS assays recognized the S249C/TACC3v1 fusion as a S249C mutation only as this fusion was below detection threshold.

• For information regarding other commercially available FGFR tests or laboratory developed tests, please speak with the pathologist at your institution or contact the manufacturer of the test.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 17 December 2024.