Erdafitinib did not outperform pembrolizumab as second-line treatment for metastatic urothelial carcinoma.
Despite much progress in first-line treatment of metastatic urothelial cancer, second-line treatment remains an unmet clinical need.1 Selective fibroblast growth factor receptor (FGFR) inhibition is becoming an increasingly important focus of novel drug development for this population.2 Erdafitinib is a US-approved oral pan-FGFR tyrosine kinase inhibitor to treat locally advanced/metastatic urothelial carcinoma in patients with susceptible FGFR3/2 alterations who progressed after platinum-containing chemotherapy. Erdafitinib’s accelerated approval was based on outcomes from a phase 2, single-arm trial.3
The recent phase 3, randomized THOR trial (NCT03390504) investigates the efficacy of erdafitinib in second-line versus standard of care in participants with unresectable, advanced or metastatic urothelial cancer. Results from Cohort 1 showed that erdafitinib significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus chemotherapy in participants with an FGFR alteration.4 In the current Cohort 2, erdafitinib was compared to pembrolizumab in the same patient group. Dr. Arlene Siefker-Radtke of MD Anderson Cancer Center, Houston, presented the results.5
Cohort 2 enrolled 351checkpoint-inhibitor-naïve participants who had progressed on first-line treatment. Participants were randomized 1:1 to erdafitinib or pembrolizumab. The primary endpoint was OS.
“In contrast to the results from Cohort 1, the trial did not meet its primary endpoint for Cohort 2,” summarized Dr. Siefker-Radtke. Neither the median OS nor the median PFS were statistically different between the two groups. “This was somewhat unexpected because FGFR-altered tumors are known as ‘cold’ tumors, i.e., unresponsive for immune therapy. In line with this, we observed a significantly lower ORR in participants treated with pembrolizumab. However, the duration of response was longer in the pembrolizumab arm than in the erdafitinib arm.”
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