Final Analysis of a Noninterventional Study on Cabozantinib in Patients With Advanced Renal Cell Carcinoma After Prior Checkpoint Inhibitor Therapy of the German Interdisciplinary Working Group on Renal Tumors (IAG-N)

Clin Genitourin Cancer. 2024 Oct;22(5):102159. doi: 10.1016/j.clgc.2024.102159. Epub 2024 Jul 8.

Abstract

Background: Efficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC).

Objective: To evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies.

Design, setting and participants: Patients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany.

Interventions: Cabozantinib was administered as a standard of care.

Outcome measurements and statistical analysis: Adverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized.

Results and limitations: About 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study.

Conclusions: Cabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment.

Keywords: Cabozantinib; Immune checkpoint inhibitor; Immune refractory; Metastatic renal cell carcinoma; Previously treated patients.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anilides* / administration & dosage
  • Anilides* / adverse effects
  • Anilides* / therapeutic use
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / pathology
  • Female
  • Germany / epidemiology
  • Humans
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / pathology
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines* / administration & dosage
  • Pyridines* / adverse effects
  • Pyridines* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • cabozantinib
  • Anilides
  • Pyridines
  • Protein Kinase Inhibitors