Erdafitinib outperforms chemotherapy in FGFR-altered advanced urothelial cancer

Patients with FGFR-altered advanced urothelial cancer who progressed after 1 or 2 lines of anti-PD-(L)1 treatment benefitted from the pan-FGFR tyrosine kinase inhibitor erdafitinib in the phase 3 THOR trial.

Checkpoint inhibitors are standard-of-care both in first-line and second-line setting in patients with advanced or metastatic urothelial cancer [1]. Treatment options after progression on checkpoint inhibitors are limited and only 30% of patients receive subsequent anti-cancer treatment after anti-PD-(L)1 treatment [2]. FGFR gene alterations are common in advanced/metastatic urothelial cancer, and the pan-FGFR tyrosine kinase inhibitor erdafitinib showed promising clinical activity in a single-arm phase 2 trial [3].

THOR (NCT03390504) is a randomised, confirmatory, phase 3 trial assessing whether erdafitinib improves survival over chemotherapy in patients with FGFR-altered advanced/metastatic urothelial cancer who progressed on or after 1 or more prior lines of treatment including anti-PD-(L)1 therapy. Dr Yohann Loriot (Gustave Roussy Cancer Institute, France) presented the results [4].

The study randomised 266 participants 1:1 to receive erdafitinib or chemotherapy (i.e. docetaxel or vinflunine); 78 participants had received 1 prior line of treatment, and 187 had received 2 prior lines of treatment. The primary endpoint was overall survival (OS); key secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and safety.

The study met its primary endpoint. The median OS for erdafitinib was superior to chemotherapy: 12.1 versus 7.8 months (HR 0.64; P=0.0005). The OS benefit of erdafitinib was seen across all subgroups. In addition, erdafitinib significantly improved median PFS: 5.6 versus 2.7 months (HR 0.58; P=0.0002). ORR in the erdafitinib arm was 45.6% (6.6% complete responders) compared with 11.5% (0.8% complete responders) in the chemotherapy arm.

Safety profiles were consistent with the known profiles of erdafitinib and chemotherapy. Of patients treated with erdafitinib, 8.1% discontinued therapy due to treatment-related adverse events. Of patients treated with chemotherapy, 13.4% discontinued therapy due to treatment-related adverse events. Adverse events of interest in the erdafitinib arm were nail, skin, and eye disorders, and central serous retinopathy.

“The results of the THOR trial support the clinical efficacy of erdafitinib as the standard-of-care option for patients with advanced/metastatic FGFR-altered urothelial cancer after anti-PD-(L)1 treatment. In addition, these results support molecular testing for FGFR alterations in all patients with advanced/metastatic urothelial cancer,” concluded Dr Loriot.

1. Rhea LP, et al. Clin Med Insight Oncol. 2021;15:11795549211044963.
2. Morgans AK, et al. Clin Genitourin Cancer. 2022;20:543–552.
3. Loriot Y, et al. N Engl J Med 2019;381:338–348.
4. Loriot Y, et al. Phase 3 THOR study: results of erdafitinib versus chemotherapy in patients with advanced or metastatic urothelial cancer with selected fibroblast growth factor receptor alteration. Abstract LBA4619, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

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Posted on 2 August 202317 May 2024