Neutrophil to lymphocyte ratio and response to tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma.

477 Background: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are markers of host inflammation and have prognostic value in many solid tumors. Here we aimed to explore the association of NLR and PLR with response to tyrosine kinase inhibitor (TKI) treatment in metastatic renal cell carcinoma (mRCC). Methods: Data from patients with mRCC treated at the Princess Margaret Cancer Centrein Toronto with a TKI as first-line treatment were retrospectively collected. The association of several variables with response to treatment (complete response [CR] or partial response [PR] vs. stable disease > 3 months [SD] or progressive disease [PD]) was assessed by binary logistic regression. Significant variables were dichotomized and cut-offs selected by the area under the receiver operating characteristic (AUC) curve. Results: Data from 157 patients treated between 11/2004 and 09/2012 were analyzed. Median age at start of TKI treatment was 61 years and first-line treatment was sunitinib, sorafenib, and other in 49%, 43%, and 8% of patients, respectively. Best response was CR/PR, SD, and PD in 27%, 55%, and 18% patients. On multivariable analysis NLR > 2.5 and Karnofsky Performance Status (KPS) < 90% were associated with a lower likelihood of response and each allocated a score of 1 unit. Response rates for a score of 0, 1, or 2 were 45% (29-61%), 28% (17-38%), 10% (1-19%), respectively. PLR did not retain association with response in multivariable analysis. Conclusions: NLR and KPS are associated with response to TKI treatment in mRCC. Data from an external validation set will also be presented.

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Association of hypothyroidism with improved outcomes in first-line treatment of renal cell carcinoma with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.466 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 466-466 ◽

Cited By ~ 2

Author(s):

Flavio Augusto Ismael Pinto ◽

Augusto Akikubo Rodrigues Pereira ◽

Maria Nirvana Formiga ◽

Marcello Ferretti Fanelli ◽

Ludmilla T. D. Chinen ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Prognostic Factors ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitor ◽

Univariate Analysis ◽

Intermediate Risk ◽

Line Treatment ◽

First Line ◽

First Line Treatment

466 Background: Sunitinib, a multitarget tyrosine-kinase inhibitor, has become a standard of care for first-line low and intermediate risk metastatic renal cell carcinoma (mRCC). Sunitinib-induced hypothyroidism and hypertension have been correlated with better outcomes in those patients. Methods: Fifty patients with mRCC, treated in the first-line with sunitinib, were retrospective analyzed at one brazilian institution, for overall survival (OS), progression free survival (PFS), overall response rate (ORR) and toxicity. We evaluated clinical and laboratory parameters, such as hypothyroidism (TSH level > 5,5 mIU/L) and hypertension, to identify prognostic factors. Results: The median age of patients was 58 years (range: 37-73 years), 82% were male, 54% were ECOG 0 or 1, and 76% were classified in low or intermediate risk. Nefrectomy was performed in 96% of cases. Lung and bone were the most common sites of metastases. The incidence of hypothyroidism and hypertension during treatment were 40% and 34%, respectively. ORR for the entire population was 40% and it was statistically superior in patients that developed hypothyroidism during treatment (90% vs. 20%; p<0,0001). Median survival and PFS were 21.7 months (10.65-17.70 months, 95% CI) and 14.2 months (15.77-27.58 months, 95% CI), respectively. In univariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001), hypothyroidism (p<00001) and hypertension (p=0,001) were associated with OS. In multivariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001) and hypothyroidism (p<00001) were independent prognostic factors for OS. The most common severe adverse events (G3-4) were asthenia (14%), diarrhoea (6%), neutropenia (14%), thrombocytopenia (10%), hand-foot syndrome (6%) and hypertension (8%). Conclusions: Efficacy in survival and toxicity profile of sunitinib in first-line treatment of mRCC in patients out of clinical trials were comparable to prior studies. Hypothyroidism, MSKCC criteria and ECOG were independent prognostic factors for survival.

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miR-9-5p in Nephrectomy Specimens is a Potential Predictor of Primary Resistance to First-Line Treatment with Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma

Cancers ◽

10.3390/cancers10090321 ◽

2018 ◽

Vol 10 (9) ◽

pp. 321 ◽

Cited By ~ 4

Author(s):

Bernhard Ralla ◽

Jonas Busch ◽

Anne Flörcken ◽

Jörg Westermann ◽

Zhongwei Zhao ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Tyrosine Kinase ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Line Treatment ◽

First Line ◽

Primary Resistance ◽

Tki Treatment ◽

First Line Treatment

Approximately 20–30% of patients with metastatic renal cell carcinoma (mRCC) in first-line treatment with tyrosine kinase inhibitors (TKIs) do not respond due to primary resistance to this drug. At present, suitable robust biomarkers for prediction of a response are not available. Therefore, the aim of this study was to evaluate a panel of microRNAs (miRNAs) in nephrectomy specimens for use as predictive biomarkers for TKI resistance. Archived formalin-fixed, paraffin embedded nephrectomy samples from 60 mRCC patients treated with first-line TKIs (sunitinib, n = 51; pazopanib, n = 6; sorafenib, n = 3) were categorized into responders and non-responders. Using the standard Response Evaluation Criteria in Solid Tumors, patients with progressive disease within 3 months after the start of treatment with TKI were considered as non-responders and those patients with stable disease and complete or partial response under the TKI treatment for at least 6 months as responders. Based on a miRNA microarray expression profile in the two stratified groups of patients, seven differentially expressed miRNAs were validated using droplet digital reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) assays in the two groups. Receiver operating characteristic curve analysis and binary logistic regression of response prediction were performed. MiR-9-5p and miR-489-3p were able to discriminate between the two groups. MiR-9-5p, as the most significant miRNA, improved the correct prediction of primary resistance against TKIs in comparison to that of conventional clinicopathological variables. The results of the decision curve analyses, Kaplan-Meier analyses and Cox regression analyses confirmed the potential of miR-9-5p in the prediction of response to TKIs and the prediction of progression-free survival after the initiation of TKI treatment.

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Comparative efficacy of sunitinib versus sorafenib as the first-line treatment for patients with metastatic renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15080 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15080-e15080

Author(s):

Seongjoon Park ◽

Jae-Lyun Lee ◽

Inkeun Park ◽

Kwonoh Park ◽

Yongchel Ahn ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitor ◽

Comparable Efficacy ◽

Line Treatment ◽

First Line ◽

Grade 3 ◽

First Line Treatment

e15080 Background: Currently, sunitinib has been recommended as the primary treatment in the patients with metastatic renal cell carcinoma (mRCC) among the vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). However, there are no published clinical data that compared directly the efficacy of targeted agents in the first line setting, and first-line treatment in mRCC patients is yet to be determined. Methods: To compare the efficacy and toxicities between sorafenib and sunitinb, clinical database was used to identify all patients with mRCC treated with VEGF TKIs in Asan Medical Center from April 2005 to March 2011. Among 304 patients, we identified 49 and 220 patients who were treated first with sorafenib and sunitinib, respectively. Results: The patients in the sorafenib group were older than those in the sunitinib group (62 vs 56.5 years, p=0.019). Disease control rate (DCR) of 82% was achieved in both groups. After a median follow-up duration of 49 months, progression free survival (PFS) and overall survival (OS) were not significantly different (sorafenib vs sunitinib, PFS; 8.6 months vs 9.9 months, p=0.948, OS; 25.7 months and 22.6 months, p=0.774). The patients treated with sorafenib have required dose reduction due to toxicities less frequently than those treated with sunitinib (37% vs 54%, p=0.034). Hematologic toxicities of grade 3 or 4 were more common in sunitinib group (4.2% vs 44.6%, p<0.001), and also was grade 3 or 4 hypertension, although it was not statistically significant (4.2% vs 13.7%, p=0.06). Age (> 60 years), duration from diagnosis to treatment (less than 1 year), Anemia, Neutrophilia, thorombocytosis, bone and liver metastases were independent prognostic factors affecting OS. Multivariate analysis also showed first-line VEGF TKI did not affect OS [hazard ratio (HR, sorafenib vs sunitinib) = 0.94, p=0.774]. Conclusions: Sorafenib showed comparable efficacy to sunitinb and demonstrated superiority in toxicities in the treatment of mRCC patients.

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