Dr Siefker-Radtke on the Efficacy of Erdafitinib vs Pembrolizumab in FGFR-Altered mUC

Arlene O. Siefker-Radtke, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the efficacy of erdafitinib (Balversa) in patients with metastatic urothelial cancer (mUC) with select FGFR alterations in the phase 3 THOR study (NCT03390504).

The oral, pan-FGFR tyrosine kinase inhibitor erdafinitib was previously approved by the FDA for the treatment of patients with locally advanced or metastatic FGFR2/3-altered mUC who have progressed after platinum-containing chemotherapy in 2019. Although erdafitinib provides these patients with a viable treatment option, the optimal sequencing of erdafitinib alongside other second-line therapeutics has been under-investigated, Siefker-Radtke states.

The randomized, open-label THOR study assessed the efficacy of erdaftinib in 2 independent cohorts. In cohort 1, patients with FGFR-altered mUC who progressed on or after at least 1 prior line of therapy, including an anti–PD-L1 inhibitor, were randomly assigned to receive erdafitinib or chemotherapy. Previously reported data from this cohort showed that the agent extended overall survival (OS) vs chemotherapy. Cohort 2 randomly assigned patients with mUC who progressed on 1 prior treatment and were naïve to anti– PD-L1 inhibitors to receive erdafitinib or pembrolizumab (Keytruda).

Results from cohort 2 were presented at the 2023 ESMO Congress, and showed that the median OS was 10.9 months with erdafitinib and 11.1 months with pembrolizumab (HR, 1.18; 95% CI, 0.9-1.5; P = 0.18.). Because no statistically significant difference in OS with erdafitinib vs pembrolizumab was observed, the primary end point of the trial was therefore not met, Siefker-Radtke reports. HRs were also similar across subgroups, she adds. Erdafitinib did exhibit numerically longer progression-free survival (PFS) of 4.4 months vs 2.7 months with pembrolizumab, as well as a numerically higher overall response rate (ORR) of 40.0% vs 21.6%, Siefker-Radtke adds. However, the duration of response was shorter with erdafitinib compared with pembrolizumab, she notes. Safety profiles were consistent with the known toxicity profiles of erdafitinib and pembrolizumab as monotherapies.

These results suggest that the sequencing of erdafitinib is important for patients with FGFR alterations in the second-line, Siefker-Radtke says. Accordingly, treatment with an immune checkpoint inhibitor prior to erdafitinib is recommended for patients who were previously exposed to chemotherapy, Siefker-Radtke advises. However, treatment decision-making should take individual patient characteristics into account, as select populations may benefit from further cytoreduction prior to treatment with immunotherapy, she concludes.