ASCO 2019: FIERCE-22: Clinical Activity of Vofatamab - FGFR3 Selective Inhibitor in Combination with Pembrolizumab in WT Metastatic Urothelial Carcinoma - Medical Oncologist Perspective

Chicago, IL (UroToday.com) FGF receptor 3 (FGFR3) alterations are frequently encountered in urothelial carcinoma, both in non-muscle invasive and muscle-invasive disease.1 For patients with muscle-invasive disease, FGFR3 mutations have been observed in 2% of primary tumors and 9% of metastases.2 FGFR inhibitors have been under evaluation for many years and recently, the FDA granted accelerated approval for erdafitinib for patients with susceptible FGFR3 or FGFR2 genetic alterations who have progressed during or following platinum-containing chemotherapy.

Early studies suggest that patients with pathogenic FGFR do not respond to immune checkpoint inhibition and another abstract being presented at ASCO by Mayhew et al shows that patients harboring pathogenic FGFR3 alterations had 0% favorable response to ICI.3 However, for patients without FGFR alterations, it is unknow if the combination of an FGFR3 inhibitor and ICI may be efficacious. This abstract provides data on 28 patients with mUC who had progressed on at least 1 line of prior therapy. Baseline characteristics are shown below.Patients were unselected with regards to PD-1 status and 25% had a Bellmunt score of greater than 1.  The safety profile was similar to prior reported studies with nausea, anemia, diarrhea, and fatigue occurring in more than 20% of the patients. In terms of response, 22 patients were evaluable and the ORR was 36% and confirmed ORR was 32% at 9 weeks. ORR was 43% for patients with FGFR mutations/fusion but this sample size was small (3/7).The clinical responses varied based on molecular subgroups. Patients with the luminal subtype had increased objective responses than those with basal or p53-like subgroup.The current sample size is small but patients with luminal subtype also appear to have a more durable response than basal and p53. A significant number of patients who did not have molecular subtyping data available had durable responses as wellThis study shows that the combination of FGFR3 inhibitor with pembrolizumab may be an effective therapy for patients with UC w/wild type FGFR3. However, this was a non-randomized study so it is unknown how single agent pembrolizumab compares against this combination. The correlative studies provide exciting data regarding the relationship of molecular subtypes and response to this combination therapy. Data here support further study of FGFR3 and immunotherapy combinations.

Presented by: Arlene O. Siefker-Radtke, MD, MD Anderson Cancer Center, Houston, TX

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu, at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References:
  1. Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Human molecular genetics 2012;22:795-803.
  2. Guancial EA, Werner L, Bellmunt J, et al. FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder. Cancer medicine 2014;3:835-44.
  3. Rose TL, Hayward MC, Salazar AH, et al. Fibroblast growth factor receptor status and response to immune checkpoint inhibition in metastatic urothelial cancer. Journal of Clinical Oncology 2019;37:458-.

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