(UroToday.com) The 2022 GU ASCO Annual meeting included a urothelial carcinoma session highlighting work from Dr. Vadim Koshkin and colleagues presenting preliminary results of futibatinib plus pembrolizumab in patients with advanced or metastatic urothelial carcinoma.
Immune checkpoint inhibitors (ICIs), including pembrolizumab, are among the few treatment options available for platinum-ineligible patients with metastatic urothelial carcinoma, but only 25–30% of patients achieve responses with ICIs. FGFR DNA alterations (in 15–20% of metastatic urothelial carcinomas) may contribute to poor responses to ICIs, and FGFR inhibition may sensitize tumors to ICIs by direct action on cancer cells or by altering the tumor microenvironment. In an open-label phase 2 study (NCT04601857), futibatinib, a highly selective, potent, irreversible FGFR1–4 inhibitor with activity in FGFR-deregulated tumors, is being assessed in combination with pembrolizumab in patients with metastatic urothelial carcinoma. At GU ASCO 2022, Dr. Koshkin reported the preliminary findings from the safety lead-in phase.
Eligible patients (≥18 y; ECOG PS ≤1) had metastatic urothelial carcinoma, were treatment naive in the advanced/metastatic setting, and unfit for, intolerant to, or refusing platinum-based chemotherapy. Prior anti–PD-1/PD-ligand 1/2 or FGFR inhibitor therapy were not permitted. Patients (regardless of FGFR alteration status) were first enrolled in a safety lead-in and received futibatinib 20 mg orally once daily and pembrolizumab 200 mg IV every 21 days. Dose-limiting toxicities were assessed during the first 21-day treatment cycle. The trial schema for this phase 2 study is as follows:
As of December 13, 2021, 10 patients were enrolled in the safety lead-in. Median age was 73.0 years (range, 46–84 y) and 20% of patients had an ECOG performance of 1. Median duration of treatment was 34.5 days (range: 1–197 days) with futibatinib and 35 days (range: 1–197 days) with pembrolizumab. Adverse events were reported in 90% of patients; adverse events in > 2 among all patients were diarrhea (50%), hyperphosphatemia (50%), increased aspartate aminotransferase (50%), and pruritus (50%). Grade 3 adverse events were reported in 6 patients: increased ALT and fatigue (20% each) and decreased appetite and diarrhea (10% each). There were no grade 4–5 adverse events. There were 8/10 patients evaluated for dose-limiting toxicities after 1 treatment cycle, and no dose-limiting toxicities were reported.
Dr. Koshkin concluded this presentation of futibatinib plus pembrolizumab in patients with advanced or metastatic urothelial carcinoma with the following take-home messages:
- Preliminary safety results support tolerability of futibatinib plus pembrolizumab in platinum-ineligible patients with metastatic urothelial carcinoma
- As no dose-limiting toxicities were observed in the safety lead-in, the recommended dose of futibatinib in combination with pembrolizumab is 20 mg days
- Enrollment in patients is ongoing to evaluate the efficacy and safety of futibatinib in combination with pembrolizumab
Co-Authors: Guru P. Sonpavde, Clara Hwang, Begona Mellado, Gareth Tomlinson, Masashi Shimura, Michael Jon Chisamore, Maciej Gil, Yohann Loriot
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022