Abstract
Simple SummarySecond-line systematic therapy options for soft-tissue sarcoma (STS) have remained unchanged for decades due to the rarity and various histological types associated with STS. Challenges with molecular-targeted treatments for STS led to the approval of pazopanib and its wide use for STS. However, predictive markers of pazopanib treatment for STS have not been identified. Baseline neutrophil-to-lymphocyte ratio (NLR) is known as a candidate biomarker for several cancers. In this retrospective study, we investigated the use of the NLR as a predictor for the efficacy and prognosis of pazopanib in patients with STS. Our findings could be useful for the development of biomarker-targeted therapies for STS.Pazopanib with trabectedin and eribulin is widely used to treat soft-tissue sarcoma (STS). We have shown that baseline neutrophil-to-lymphocyte ratio (NLR) may predict the efficacy and patient prognosis of eribulin. Changes in NLR, but not baseline NLR, can predict patient prognosis of trabectedin. However, prognostic factors of pazopanib for STS have not been identified. We present a retrospective analysis of 141 patients treated with pazopanib for recurrent or metastatic non-round cell STS. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit (DCB), overall survival (OS), and progression-free survival. L-sarcoma histology (odds ratio [OR] = 0.31, 95% CI = 0.12–0.79; p = 0.014) and pre-treatment NLR < 3.0 (OR = 2.03, 95% CI = 1.02–6.67; p = 0.045) were independent predictive factors of DCB. Pre-treatment NLR < 3.0 (hazard ratio [HR] = 0.55, 95% CI = 0.36–0.84; p = 0.0057), liposarcoma histology (HR = 1.78, 95% CI = 1.09–2.91; p = 0.022), primary extremity site (HR = 0.48, 95% CI = 0.31–0.75; p = 0.0010), ECOG PS ≥ 1 (HR = 1.62, 95% CI = 1.08–2.42; p = 0.019), and CRP < 0.3 (HR = 0.52, 95% CI = 0.33–0.82; p = 0.0050) were independent predictive factors of OS. These findings indicate that baseline NLR predicts the efficacy and patient prognosis of pazopanib for STS.
Highlights
Pazopanib is an oral multitargeted tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor (VEGF) receptors (VEGFR)−1, −2, and −3, platelet-derived growth factor receptors (PDGFR)-α and -β, and c-kit [1].A randomized, double-blind phase III trial (VEG105192) in treatment-naive and cytokine-pre-treated patients with advanced renal cell carcinoma (RCC) showed significant improvement of progression-free survival (PFS) and tumor response for pazopanib compared with placebo [2]
These factors were categorized as follows: age:
A total of 141 patients with non-round cell soft-tissue sarcoma (STS) were treated with pazopanib between December 2012 and December 2019
Summary
A randomized, double-blind phase III trial (VEG105192) in treatment-naive and cytokine-pre-treated patients with advanced renal cell carcinoma (RCC) showed significant improvement of progression-free survival (PFS) and tumor response for pazopanib compared with placebo [2]. From these results, pazopanib was first approved for the treatment of advanced RCC in the United States in October 2009 and in Europe in June 2010. The findings demonstrated that pazopanib had a longer median PFS of 4.6 months compared with 1.6 months for placebos (p < 0.0001) [3] These results supported the approval of pazopanib for clinical use in the United States in April 2012 and in Europe in August 2012
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