Erdafitinib Approaches EU Approval for FGFR3+ Unresectable or Metastatic Urothelial Carcinoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the marketing authorization of erdafitinib (Balversa) monotherapy for use in adult patients with FGFR3-positive unresectable or metastatic urothelial carcinoma who received at least 1 line of therapy containing a PD-(L)1 inhibitor in the unresectable or metastatic setting.¹

The positive opinion is based on findings from cohort 1 of the phase 3 THOR study (NCT03390504) in which, at a median follow-up of 15.9 months, erdafitinib (n = 136) led to a median overall survival (OS) of 12.1 months vs 7.8 months with investigator’s choice of chemotherapy (n = 130; HR, 0.64; 95% CI, 0.44-0.93; P = .0050).² The median progression-free survival (PFS) with erdafitinib was 5.6 months vs 2.7 months with chemotherapy (HR, 0.58; 95% CI, 0.41-0.82; P = .0002). The overall response rate (ORR) was 45.6%, with a complete response rate of 6.6% and a partial response rate of 39.0%; in the chemotherapy arm, these respective rates were 11.5%, 0.8%, and 10.8%.

“Today’s recommendation from the CHMP marks important progress towards transforming outcomes for patients diagnosed with bladder cancer with FGFR alterations. There is a critical need for a multidisciplinary care team approach, to identify patients who may benefit from erdafitinib through biomarker testing, ensuring the right treatment reaches the right patient at the right time,” Henar Hevia, PhD, senior director, EMEA Therapeutic Area Lead, Oncology at Johnson & Johnson Innovative Medicine, stated in a news release.¹ “Pending approval, we look forward to providing eligible patients across the region with a new treatment option as soon as possible.”

The open-label, controlled, multicenter, phase 3 THOR study enrolled patients aged 18 years with metastatic or unresectable urothelial carcinoma who received 1 to 2 lines of systemic therapy and prior treatment with a PD-(L)1 inhibitor.² Patients had confirmed disease progression, tumors harboring select FGFR3/2 mutations/fusions, and an ECOG performance status of 0 to 2.

Study participants were randomly assigned 1:1 to receive once-daily erdafitinib at a dose of 8 mg with pharmacodynamically-guided uptitration to 9 mg or investigator’s choice of chemotherapy in the form of docetaxel or vinflunine once every 3 weeks. Key stratification factors included region (North America vs European Union vs rest of the world), performance status (0 or 1 vs 2), and disease distribution (presence vs absence of visceral metastases).

OS served as the trial’s primary end point and key secondary end points comprised PFS, ORR, and safety.

Patient characteristics at baseline were generally balanced between the erdafitinib and chemotherapy arms. The median patient age across the arms was 67.5 years (range, 32-86). Most patients were male (70.6% vs 72.3%) and White (59.6% vs 48.5%). In the erdafitinib arm, visceral metastases were present in 74.3% of patients, with 22.8% located in the liver; in the chemotherapy arm, these respective rates were 74.6% and 29.2%. Most patients had an ECOG performance status ranging from 0 to 1 (erdafitinib, 91.2%; chemotherapy, 90%) and PD-L1–low disease, with a combined positive score below 10 (92.7% vs 86.1%). In the erdafitinib arm, 33.1% of patients received 1 prior line of systemic treatment and 66.2% received 2 prior lines; in the chemotherapy arm, these rates were 25.4% and 74.6%, respectively.

All patients had received anti–PD-1 therapy in the first- or second-line setting. In the erdafitinib arm, 24.3% of patients received chemotherapy plus PD-L1 inhibition as their 1 line of prior systemic therapy; 8.1% received a PD-(L)1 inhibitor, and 0.7% received chemotherapy. In the chemotherapy arm, these respective rates were 11.5%, 12.3%, and 1.5%.

Within those in the erdafitinib arm who received 2 prior lines of systemic therapy, 56.6% received chemotherapy as their first line of therapy, 4.4% received chemotherapy plus a PD-(L)1 inhibitor, and 5.1% received other treatment; these respective rates in the chemotherapy arm were 58.5%, 7.7%, and 8.5%. In the erdafitinib arm, 55.9% received a PD-(L)1 as their second line of therapy, 7.4% received chemotherapy, and 2.9% received other treatment; in the chemotherapy arm, these respective rates were 58.5%, 10.8%, and 5.4%.

The toxicity profiles proved to be consistent with what has previously been reported with erdafitinib and chemotherapy. In the erdafitinib arm (n = 135), 97.0% of patients experienced at least 1 treatment-related adverse effect (AE) and the effects were grade 3 or 4 for 45.9% of patients. The most common AEs included hyperphosphatemia (any grade, 78.5%; grade 3/4, 5.2%), diarrhea (54.8%; 3.0%), stomatitis (45.9%; 8.1%), dry mouth (38.5%; 0%), Palmar-plantar erythrodysesthesia (30.4%; 9.6%), and onycholysis (23.0%; 5.9%). Moreover, 13.3% of patients experienced treatment-related series AEs and 8.1% of treatment-related AEs led to discontinuation of the agent. One treatment-related death occurred.

“Erdafitinib has been shown to significantly improve outcomes for patients with FGFR3-altered urothelial carcinoma based on the THOR study results and represents an important new therapeutic option for these patients,” Kiran Patel, MD, vice president of Clinical Development, Solid Tumours at Johnson & Johnson Innovative Medicine, added in the news release.¹ “We are dedicated to advancing precision medicine approaches in oncology to improve patient outcomes, and this positive CHMP opinion is a significant milestone in our efforts to combat bladder cancer.”

References

1. CHMP adopts positive opinion for BALVERSA (erdafitinib) for the treatment of adult patients with unresectable or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations. News release. Janssen Cilag International NV. June 28, 2024. Accessed June 28, 2024. https://www.globenewswire.com/news-release/2024/06/28/2905783/0/en/CHMP-adopts-positive-opinion-for-BALVERSA-erdafitinib-for-the-treatment-of-adult-patients-with-unresectable-or-metastatic-urothelial-carcinoma-with-susceptible-FGFR3-genetic-altera.html
2. Loriot Y, Matsubara N, Park SH, et al. Phase 3 THOR study: results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt). J Clin Oncol. 2023;41(suppl 17):LBA4619. doi:10.1200/JCO.2023.41.17_suppl.LBA4619