KEY TAKEAWAYS
- PROOF 302 is a phase III randomized, double-blind, placebo-controlled adjuvant trial.
- The primary aim is to determine the disease-free survival of patients with high-risk muscle-invasive upper tract or urothelial bladder cancer with susceptible FGFR3 alterations.
- Eligible patients are given oral infigratinib 125 mg or placebo daily for up to 52 weeks after radical surgery.
- The trial’s primary outcome measure is centrally determined DFS, while secondary outcome measures include investigator-assessed DFS, metastasis-free survival, OS, and safety/tolerability.
- This study will define the role of infigratinib as a potential treatment option for patients with cancers of the bladder and urinary system who also have FGFR3 alterations, where more treatment options are needed.
Approximately 218 patients from 120 centers across the globe are participating in the PROOF 302 trial (NCT04197986), a randomized, double-blind, placebo-controlled, adjuvant phase III study. Patients must meet the following inclusion criteria: ≤ 120 days after radical surgery; ineligible for or refusing cisplatin-based (neo)adjuvant chemotherapy; high-risk muscle-invasive upper-tract urothelial cancer (85% of patients) or urothelial bladder cancer (15%); and susceptible FGFR3 alterations (activating mutations, gene fusions, or rearrangements). For up to 52 weeks, or until recurrence, unacceptable toxicity, or death, patients take either 125 mg of oral infigratinib or a placebo on days 1-21 of a 28-day cycle. Centrally determined disease-free survival (DFS) is the primary endpoint, with investigator-assessed DFS, metastasis-free survival, overall survival, and safety and tolerability serving as secondary endpoints and correlative biomarker analysis, quality of life, and pharmacokinetics of infigratinib serving as exploratory endpoints.
Urinary system cancers, especially those that are invasive and grow into the muscle layer, may require additional treatment after tumor removal, especially if the cancer has a high risk of returning. Postoperatively, chemotherapy regimens containing cisplatin are commonly used, though some patients cannot tolerate or refuse this treatment. The FGFR3 gene codes for a protein frequently altered in these malignancies. As a result, the tumor expands. The experimental drug infigratinib blocks the growth of the tumor by focusing on FGFR3. To test the efficacy of infigratinib, patients in the PROOF 302 study are given either the active drug or a placebo for an entire year following surgery. This study compares the duration of disease-free survival between infigratinib- and placebo-treated patients. Overall survival rates and times between cancer recurrences will also be measured. The study will also look into how painless and safe the treatment is. Patients with bladder and urinary system cancers with FGFR3 changes require more treatment options, making PROOF 302 a crucial study.
Source: https://pubmed.ncbi.nlm.nih.gov/35608106/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT04197986
Pal SK, Somford DM, Grivas P, Sridhar SS, Gupta S, Bellmunt J, Sonpavde G, Fleming MT, Lerner SP, Loriot Y, Hoffman-Censits J, Valderrama BP, Andresen C, Schnabel MJ, Cole S, Daneshmand S. Targeting FGFR3 alterations with adjuvant infigratinib in invasive urothelial carcinoma: the phase III PROOF 302 trial. Future Oncol. 2022 Jul;18(21):2599-2614. doi: 10.2217/fon-2021-1629. Epub 2022 May 24. PMID: 35608106.
