Intrinsic resistance to sunitinib in patients with metastatic renal cell carcinoma

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Sung Hee Lim1, In Gyu Hwang2, Jun Ho Ji3

  • 1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Asia-Pacific Journal of Clinical Oncology
|April 1, 2016
PubMed
Abstract

Insights

Intrinsic resistance to sunitinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, impacts 25% of metastatic renal cell carcinoma (mRCC) patients, leading to poorer survival outcomes. Identifying high-risk factors is crucial for treatment strategies.

Area of Science:

  • Oncology
  • Pharmacology
  • Translational Research

Background:

  • Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors like sunitinib are effective in treating metastatic renal cell carcinoma (mRCC).
  • However, a subset of mRCC patients exhibits primary or intrinsic resistance to sunitinib, limiting treatment efficacy.
  • The mechanisms underlying this intrinsic resistance remain incompletely understood.

Purpose of the Study:

  • To identify baseline parameters associated with intrinsic resistance to first-line sunitinib in mRCC patients.
  • To evaluate the prognostic impact of intrinsic resistance on patient survival outcomes.
  • To inform clinical decision-making and future research directions for sunitinib-refractory mRCC.

Main Methods:

  • A cohort of 134 mRCC patients treated with first-line sunitinib between 2008 and 2012 was analyzed.
  • Patients classified as having progressive disease as their best response were defined as intrinsically resistant.
  • Univariate and multivariate logistic regression analyses were performed on baseline clinical parameters.

Main Results:

  • Intrinsic resistance to sunitinib was identified in 33 (25%) of the analyzed mRCC patients.
  • Multivariate analysis revealed that the number of metastatic sites (OR=3.6) and neutrophilia (OR=7.4) were independent predictors of intrinsic resistance.
  • Patients with intrinsic resistance showed significantly worse overall survival (P=0.001) and progression-free survival (P<0.0001).

Conclusions:

  • Intrinsic resistance to first-line sunitinib is linked to a poor prognosis in mRCC.
  • High-risk factors such as poor performance, neutrophilia, elevated lactate dehydrogenase, and liver metastases may predict limited benefit from sunitinib.
  • Further research into the molecular mechanisms and biomarkers for detecting intrinsic resistance is warranted.
Keywords:
intrinsic resistanceprognosisrenal cell carcinomasunitinib

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