No benefit of erdafitinib over pembrolizumab in urothelial cancer second-line therapy

While superior to chemotherapy, erdafitinib did not outperform pembrolizumab as second-line treatment in participants with FGFR3/2-altered, metastatic urothelial carcinoma, results from Cohort 2 of the THOR trial showed.

Despite much progress in first-line treatment of metastatic urothelial cancer, improved second-line treatment remains an unmet clinical need [1]. Selective 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, randomised THOR trial (NCT03390504) investigates the efficacy of erdafitinib as a second-line treatment 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 with pembrolizumab in the same participant group. Prof. Arlene Siefker-Radtke (MD Anderson Cancer Centre, TX, USA) presented the results [5].

Cohort 2 enrolled 351 (checkpoint inhibitor-naïve) participants who had progressed on first-line treatment. Participants were randomised 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,” summarised Prof. Siefker-Radtke. Neither the median OS nor the median PFS were statistically different between the groups. She continued: “This was somewhat unexpected because FGFR-altered tumours are known as ‘cold’ tumours, 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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   1. Zheng X, et al. Front Oncol. 2022;12:907377.
   2. Garje R, et al. Oncologist. 2020;25(11):e1711–e1719.
   3. Loriot Y, et al. N Engl J Med. 2019;381:338–348.
   4. Loriot Y, et al. J Clin Oncol. 2023;41(17_suppl):LBA4619–LBA4619.
   5. Siefker-Radtke AO, et al. Phase III THOR study: Results of erdafitinib (erda) vs pembrolizumab (pembro) in pretreated patients (pts) with advanced or metastatic urothelial cancer (muc) with select fibroblast growth factor receptor alterations (FGFRalt). Abstract 2359O, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 19 December 202319 December 2023