First-line axitinib therapy is less effective in metastatic renal cell carcinoma with spindle histology

Kazuyuki Numakura,Yumina Muto,Soki Kashima,Yuya Sekine,Tomonori Habuchi,Shintaro Narita,Mizuki Kobayashi,Ryohei Yamamoto,Hiroshi Nanjyo,Taketoshi Nara,Mitsuru Saito,Atsushi Koizumi,Makoto Takahashi

doi:10.1038/s41598-020-77135-6

Kazuyuki Numakura, Yumina Muto + Show 11 more

Open Access

https://doi.org/10.1038/s41598-020-77135-6

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Journal: Scientific Reports	Publication Date: Nov 18, 2020
Citations: 5	License type: open-access

Affiliation: Akita University, Akita University Hospital

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.

Highlights

Axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor, will be used in combination first-line therapies against metastatic renal cell carcinoma, but its effects as a first-line monotherapy are unclear
Immune combination therapy has not shown a clear advantage over vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy in patients with metastatic renal cell carcinoma (mRCC) that have favorable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk s cores[1,2,3]
Cox regression analyses for clinical predictors revealed that high C-reactive protein (CRP) value was significantly correlated with shorter progression-free survival (PFS) (HR, 1.63; 95% confidence interval (CI) 1.7–4.0), whereas spindle histology and poor IMDC risk score were correlated with worse overall survival (OS) (HR, 2.87 and 2.88, respectively; 95% CI 1.4–11.0 and 1.1–8.5, respectively) (Table 4)

Summary

Introduction

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. Abbreviations ICI Immune checkpoint inhibitors CTLA-4 Cytotoxic T-lymphocyte associated antigen-4 mRCC Metastatic renal cell carcinoma VEGFR Vascular endothelial growth factor receptor TKI Tyrosine kinase inhibitor IMDC International Metastatic Renal Cell Carcinoma Database Consortium ECOG Eastern Cooperative Oncology Group PS Performance status ORR Objective response rate PFS Progression-free survival OS Overall survival AE Adverse event NLR Neutrophil–lymphocyte ratio CRP C reactive protein HR Hazard ratio CI Confidence interval. An advancement in combination therapy using immune checkpoint inhibitors (ICI) with axitinib, which is a vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI), or anti-cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) antibody would provide a standard first-line therapy in treatment of metastatic renal cell carcinoma (mRCC)[1,2,3]. The combination is expected to provide a synergistic effect[8,9], but information on outcomes of first-line axitinib monotherapy against mRCC in the subset of patients with favorable or intermediate IMDC risk scores is still needed

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