(UroToday.com) The 2024 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Monty Pal discussing the primary disease free survival analysis of the PROOF302 phase 3 randomized study assessing infigratinib versus placebo in patients with resected urothelial cancer with FGFR3 mutations or fusions. In the subset of patients with urothelial carcinoma bearing alterations in the fibroblast growth factor 3 (FGFR3) gene, targeted therapies directed at this moiety have shown substantial antitumor effect in the metastatic setting. Thus, Dr. Pal and colleagues examined infigratinib, a potent and selective inhibitor of FGFR3, as adjuvant therapy in patients with high-risk resected urothelial carcinoma.
This was an international, multicenter, phase III clinical trial, that randomly assigned patients in a 1:1 ratio to receive either oral infigratinib (125 mg) or placebo daily for 21 days of a 28-day treatment cycle, for a maximum of 13 cycles or until disease recurrence. Eligible patients had confirmed invasive urothelial carcinoma with susceptible FGFR3 alterations and had undergone radical surgery within 120 days of randomization. The primary endpoint of the study was centrally assessed disease-free survival, with secondary endpoints including investigator-assessed disease free survival, metastasis-free survival, and overall survival.
Despite intensive efforts to enroll approximately 218 patients (with 822 patients consented to molecular pre-screening), only 39 patients were enrolled, including 20 and 19 patients randomized to receive infigratinib and placebo, respectively. The frequency of FGFR3 alteration was significantly lower than anticipated, occurring in only 19% of patients overall. Mutations were observed in 13% of patients with lower tract urothelial carcinoma and 30% of patients with upper tract urothelial carcinoma. There were no significant differences observed in disease free survival, metastasis-free survival or overall survival, and more frequent grade 3/4 adverse events were noted in the experimental arm (35% versus 16%). No fatal adverse events were observed in this trial
Dr. Pal concluded his presentation discussing the primary disease free survival analysis of the PROOF302 phase 3 randomized study with the following take-home points:
- There was a failure to accrue sufficient patients to the current trial, precluding any definitive conclusions around the role of infigratinib as adjuvant therapy for FGFR3-altered urothelial carcinoma
- In the process of study conduct, however, substantial insights were garnered that may aid in the development of future precision oncology trials for adjuvant urothelial carcinoma
Presented by: Sumanta K. Pal, MD, FASCO, City of Hope Comprehensive Cancer Center, Duarte, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024