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Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in

Rafee Talukder1, Dimitra Rafailia Bakaloudi2, Dimitrios Makrakis3

  • 1Department of Medicine, University of Washington, Seattle, WA; Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX.

Clinical Genitourinary Cancer
|January 11, 2025
PubMed
Abstract

Insights

Genomic alterations in FGFR2/3, MTAP, and ERBB2 impact outcomes for advanced urothelial carcinoma (aUC) patients treated with immune checkpoint inhibitors (ICIs). ERBB2 alterations correlate with improved survival, while FGFR2/3 alterations are associated with shorter progression-free survival.

Area of Science:

  • Oncology
  • Genomics
  • Immunotherapy

Background:

  • Genomic alterations in FGFR2/3, MTAP, and ERBB2 are actionable targets in advanced urothelial carcinoma (aUC).
  • These alterations may influence the tumor microenvironment and patient response to immune checkpoint inhibitors (ICIs).

Purpose of the Study:

  • To investigate the impact of FGFR2/3, MTAP, and ERBB2 alterations on outcomes in patients with aUC treated with ICIs.
  • To identify potential biomarkers for ICI therapy in aUC.

Main Methods:

  • A multi-institution cohort of aUC patients with available genomic data treated with ICI was analyzed.
  • Outcomes including observed response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with and without specific genomic alterations.
  • Statistical analyses included logistic regression for ORR and Cox proportional hazards models for PFS and OS.

Main Results:

  • FGFR2/3 alterations were associated with lower ORR (21% vs. 32%) and significantly shorter PFS (HR=1.36, P=0.03) with ICI.
  • MTAP alterations showed a trend towards lower ORR (25% vs. 40%) but did not significantly impact PFS or OS.
  • ERBB2 alterations were linked to similar ORR (37% vs. 35%) but significantly longer PFS (HR=0.63, P=0.03) and OS (HR=0.66, P=0.03) with ICI treatment.

Conclusions:

  • FGFR2/3 alterations may predict poorer response to ICIs in aUC.
  • ERBB2 alterations appear to be a positive predictive biomarker for ICI therapy in aUC.
  • Further evaluation of FGFR2/3, MTAP, and ERBB2 alterations as biomarkers for ICI treatment in aUC is warranted.
Keywords:
BiomarkerBladder cancerImmunotherapyTumor microenvironment

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