Erdafitinib Benefits PFS, ORR in Patients With mUC Naïve to Anti-PD-L1

The phase 3 THOR study began in 2018 to examine the efficacy of erdafitinib versus pembrolizumab in patients with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt).

At the European Society for Medical Oncology Congress 2023, Dr. Arlene O. Siefker-Radtke, of the MD Anderson Cancer Center, presents results from a cohort of the THOR study that examined erdafitinib versus pembrolizumab in patients with mUC who were naïve to anti-PD-L1. While erdafitinib is a pan-FGFR tyrosine kinase inhibitor, FGFRalt tumors are enriched in luminal 1 subtype and may have limited clinical benefit from anti-PD-L1 treatment.

The cohort involved patients 18 years of age or older who had unresectable advanced/mUC with select FGFR3/2alt, an Eastern Cooperative Oncology Group performance status of 0-2, disease progression on 1 prior treatment, and were naïve to anti-PD-L1. Patients were randomized 1:1 to receive either erdafitinib 8 mg once per day with pharmacodynamically guided titration up to 9 mg, or pembrolizumab 200 mg every 3 weeks.

The primary end point was overall survival (OS), while secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. At the data cutoff in January 2023, the intent-to-treat group consisted of 175 patients in the erdafitinib arm and 176 patients in the pembrolizumab arm. Median follow-up was 33.2 months.

The primary end point of OS was not met, and there was no significant difference in OS between treatment arms. While erdafitinib provided numerically longer PFS and higher ORR, it had a shorter duration of response. The most common treatment-related adverse events (TRAEs) of any grade in the erdafitinib arm included hyperphosphatemia (73%), stomatitis (45%), diarrhea (45%), and dry mouth (35%), while patients in the pembrolizumab arm experienced pruritus (12%), asthenia (10%), hypothyroidism (10%), and fatigue (10%).

Grade 3-4 and serious TRAEs occurred in 43% and 13% of patients in the erdafitinib arm and 12% and 10% of patients in the pembrolizumab arm, respectively. TRAEs resulting in death occurred in no patients who received erdafitinib and 3 patients (2%) who received pembrolizumab. A total of 15% of patients discontinued erdafitinib treatment and 5% discontinued pembrolizumab treatment due to TRAEs.

In the THOR study’s anti-PD-L1-naïve, FGFRalt mUC patient population, erdafitinib demonstrated a longer PFS and higher ORR rate, while both erdafitinib and pembrolizumab had similar OS rates. Toxicities were manageable with dose modifications.