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Phase II Study of Erdafitinib in Patients With Tumors With FGFR Amplifications: Results From the NCI-MATCH ECOG-ACRIN
Jun Gong1, Alain C Mita1, Zihan Wei2
1Cedars-Sinai Medical Center, Los Angeles, CA.
Purpose:
Despite fibroblast growth factor receptor (FGFR) inhibitors being approved in tumor types with select FGFR rearrangements or gene mutations, amplifications of FGFR represent the most common FGFR alteration across malignancies. Subprotocol K1 (EAY131-K1) of the National Cancer Institute-MATCH platform trial was designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 amplification.
Methods:
EAY131-K1 was an open-label, single-arm, phase II study with central confirmation of presence of FGFR1-4 amplification in tumors. Patients with urothelial carcinoma were excluded. Enrolled patients received oral erdafitinib at a starting dose of 8 mg once daily continuously with escalation to 9 mg once daily continuously, on the basis of predefined time point assessments of phosphate levels, until disease progression or intolerable toxicity. The primary end point was centrally assessed objective response rate (ORR), with key secondary end points being 6-month progression-free survival (PFS6), PFS, overall survival (OS), and safety.
Results:
Thirty-five patients were enrolled into this study with 18 included in the prespecified primary efficacy analysis. The median age of the 18 patients was 60 years, and 78% had received ≥3 previous lines of therapy. There were no confirmed responses to erdafitinib; however, five patients experienced stable disease (SD) as best response. One patient with an FGFR1-amplified breast cancer had a prolonged PFS >168 days (5.5 months). The median PFS was 1.7 months (90% CI, 1.1 to 1.8 months) and the median OS was 4.2 months (90% CI, 2.3 to 9.3 months). The estimated PFS6 rate was 13.8% (90% CI, 3.3 to 31.6). The majority of toxicities were grade 1 to 2 in nature, although there was one grade 5 treatment-related adverse event.
Conclusion:
Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications. Our findings support that rearrangements and gene mutations, but not amplifications, of FGFR remain the established FGFR alterations with approved indications for FGFR inhibition.
Insights
Erdafitinib showed no significant efficacy in treating solid tumors with fibroblast growth factor receptor (FGFR) amplifications. This study suggests FGFR gene mutations and rearrangements, not amplifications, are key for FGFR inhibitor effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trials
Background:
- Fibroblast growth factor receptor (FGFR) inhibitors are approved for specific genetic alterations (rearrangements, mutations) in various cancers.
- FGFR amplifications are the most frequent FGFR alteration across malignancies, yet their therapeutic implications with inhibitors are less understood.
Purpose of the Study:
- To evaluate the antitumor efficacy of erdafitinib, an oral FGFR1-4 inhibitor, in patients with solid tumors characterized by FGFR1-4 amplification.
- To assess objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in this patient population.
Main Methods:
- An open-label, single-arm, Phase II clinical trial (EAY131-K1) was conducted.
- Patients with tumors harboring FGFR1-4 amplification (excluding urothelial carcinoma) received oral erdafitinib.
- Primary endpoint was centrally assessed ORR; secondary endpoints included PFS6, PFS, OS, and safety.
Main Results:
- Eighteen patients were included in the primary efficacy analysis; none achieved a confirmed response.
- Five patients experienced stable disease (SD) as their best response.
- Median PFS was 1.7 months, median OS was 4.2 months, and the PFS6 rate was 13.8%. One patient with FGFR1-amplified breast cancer had prolonged PFS.
Conclusions:
- Erdafitinib did not meet its primary efficacy endpoint (ORR) in patients with FGFR1-4 amplified solid tumors.
- Findings suggest that FGFR rearrangements and mutations, rather than amplifications, are the established targets for approved FGFR inhibitor therapies.
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