Pemigatinib Effective, Safe Among Patients With Unresectable or Metastatic Urothelial Carcinoma With FGFR3 Genetic Alterations

Final Results From FIGHT-201

According to final results from the phase 2 FIGHT-201 trial, pemigatinib, a selective, potent, oral inhibitor of FGFR1 through FGFR3, was well-tolerated and demonstrated clinical activity in patients with metastatic or unresectable urothelial carcinoma with FGFR3 mutations or fusions/rearrangements who had been previously treated.

Current first-line standard of care for patients with urothelial carcinoma is platinum-based chemotherapy, followed by maintenance therapy with the PD-L1 antibody avelumab for those patients who did not progress on chemotherapy. Platinum-ineligible patients may receive checkpoint inhibitors in the first-line setting.

Andrea Necchi, MD, San Raffaele University, Milan, Italy, and coauthors wrote, “Available therapies in pretreated patients can include vinflunine or taxane therapies, [checkpoint inhibitors], enfortumab vedotin, Sacituzumab govitecan (in the United States), and targeted therapies.” They added, “Fibroblast growth factor receptor 3 (FGFR3) alterations are oncogenic drivers of urothelial carcinoma.”

The open-label, single-arm, phase 2 FIGHT-201 trial enrolled 260 patients with metastatic or surgically unresectable urothelial carcinoma with FGFR3 mutations or fusions/rearrangements (cohort A; n = 204) or other FGF/FGFR alterations (cohort B; n = 56). Patients received 13.5 mg pemigatinib once daily either continuously (n = 101), or intermittently (2 weeks on/1 week off; n = 103) until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) in the continuous treatment arm of cohort A. Secondary end points included the ORR in the intermittent treatment arm of cohort A and in cohort B, the duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

The ORR of cohort A-continuous was 17.8% and 23.3% in cohort A-intermittent. Those patients harboring the most common FGFR3 mutation (S249C, n = 107) had a similar ORR across cohorts. The median DOR in both cohort A-continuous and cohort A-intermittent was 6.2 months. The median PFS was 4.0 and 4.3 months, and OS was 6.8 and 8.9 months, respectively. Pemigatinib exhibited limited clinical activity among patients in cohort B. The most common treatment-emergent adverse events were diarrhea, alopecia, stomatitis, and hyperphosphatemia.

Dr Necchi et al concluded “this phase 2 study demonstrated that pemigatinib had antitumor activity in patients with previously treated, unresectable or metastatic [urothelial carcinoma] with FGFR3 mutations or fusions/rearrangements.”

They went on to add, “These results further highlight the need for molecular testing in patients with [urothelial carcinoma] and emphasize the need to refine the biomarkers best suited for identification of targeted therapies against FGFR genomic alterations.”

Source:

Necchi A, Pouessel D, Liebowitz R, et al. Pemigatinib for metastatic or surgically unresectable urothelial carcinoma with FGF/FGFR genomic alterations: Final results from FIGHT-201. Ann Oncol. Published online November 11, 2023. doi:10.1016/j.annonc.2023.10.794