Posted: Monday, June 26, 2023
The phase III PROOF 302 trial revealed insights on the prevalence of alterations in the FGFR3 gene in patients with muscle-invasive urothelial carcinoma, based on a presentation given by Petros Grivas, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 4511). In all patients screened for this study, FGFR3 alterations were seen in 19%. Although the sponsor stopped the trial early on the use of the FGFR3 inhibitor infigratinib (also known as BGJ398) in this patient population, “the nature and frequency of co-occurring alterations in tissue samples are being investigated to help inform combination therapy strategies and putative resistance mechanisms,” the investigators noted.
A total of 617 patients with high-risk muscle-invasive urothelial carcinoma of the upper tract (n = 237) or the bladder (n = 369), or a tumor of unknown origin (n = 11), were screened using the FoundationOne platform. All patients were randomly assigned to receive treatment with the FGFR1–3 inhibitor infigratinib or a placebo. Patients received daily dosing on days 1 to 21 of a 28-day cycle.
Genomic analysis identified FGFR 1–4 alterations in 43% of patients with upper tract muscle-invasive urothelial carcinoma, 23% with muscle-invasive urothelial carcinoma of the bladder, and 9% with a tumor of unknown origin. For FGFR3 specifically, alterations were observed in 30% and 13%, respectively. Moreover, FGFR3 alterations attributable to gene insertions or deletions were present in 56% of patients with upper tract muscle-invasive urothelial carcinoma and 44% of patients with muscle-invasive urothelial carcinoma of the bladder. Furthermore, gene amplifications and structural variants accounted for 40% and 70% of the FGFR3 alterations in patients with upper tract muscle-invasive urothelial carcinoma and 60% and 30% in patients with muscle-invasive urothelial carcinoma of the bladder, respectively.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.