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Published on: February 12, 2017
First-line axitinib therapy is less effective in metastatic renal cell carcinoma with spindle histology
Kazuyuki Numakura1, Mizuki Kobayashi2, Yumina Muto2
1Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. numakura@doc.med.akita-u.ac.jp.
Abstract:
Axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor, will be used in combination first-line therapies against metastatic renal cell carcinoma (mRCC), but its effects as a first-line monotherapy are unclear. Thus, we aimed to elucidate pretreatment clinical factors that predict the prognosis of patients with mRCC receiving first-line axitinib therapy. We enrolled 63 patients with mRCC treated with axitinib as first-line therapy between Nov. 2003 and Jul. 2018. Progression-free survival (PFS) and overall survival (OS) were assessed using the Wald χ2 statistic in Cox proportional hazards regression. Median patient age was 67 (range: 25-85) years. Seven (11.1%) patients were classified as being at favorable risk, 33 (52.4%) at intermediate risk, and 23 (36.5%) at poor risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification system. Median follow-up duration after axitinib initiation was 14 (range: 1-72) months. Median PFS and OS were 18 months and 65 months, respectively. Cox regression analyses of clinical predictors revealed that high C-reactive protein (CRP) levels were significantly correlated with shorter PFS [hazard ratio (HR), 1.63; 95% confidence interval (CI) 1.7-4.0)], whereas spindle cells and poor IMDC risk scores were related to worse OS (HR, 2.87 and 2.88, respectively; 95% CI 1.4-11.0 and 1.1-8.5, respectively). Thus, patients with mRCC and spindle histology or poor IMDC risk scores had worse OS, and those with high CRP levels had shorter PFS in first-line axitinib treatment. Other therapies might be more suitable for initial management of such patients.
Insights
High C-reactive protein levels and poor International Metastatic Renal Cell Carcinoma Database Consortium risk scores predict shorter progression-free survival and overall survival in metastatic renal cell carcinoma patients receiving first-line axitinib.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Axitinib is a tyrosine kinase inhibitor used in combination therapies for metastatic renal cell carcinoma (mRCC).
- Its efficacy as a first-line monotherapy for mRCC requires further investigation.
- Predictive factors for treatment outcomes are crucial for personalized medicine.
Purpose of the Study:
- To identify pretreatment clinical factors predicting prognosis in mRCC patients receiving first-line axitinib.
- To evaluate the impact of these factors on progression-free survival (PFS) and overall survival (OS).
Main Methods:
- Retrospective analysis of 63 mRCC patients treated with first-line axitinib.
- Progression-free survival (PFS) and overall survival (OS) assessed using Cox proportional hazards regression.
- Clinical predictors including C-reactive protein (CRP) levels and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores were analyzed.
Main Results:
- Median PFS was 18 months and median OS was 65 months.
- High CRP levels correlated with shorter PFS (HR, 1.63).
- Spindle cell histology and poor IMDC risk scores were associated with worse OS (HR, 2.87 and 2.88, respectively).
Conclusions:
- High CRP levels predict shorter PFS in first-line axitinib treatment for mRCC.
- Spindle cell histology and poor IMDC risk scores predict worse OS.
- These findings suggest alternative initial therapies may be more suitable for patients with these poor prognostic indicators.

