Prognostic impact of baseline serum <scp>C</scp>‐reactive protein in patients with metastatic renal cell carcinoma (<scp>RCC</scp>) treated with sunitinib

Beuselinck, Benoît; Vano, Yann; Oudard, Stéphane; Wolter, Pascal; Smet, Robert De; Depoorter, Lore; Teghom, Corine; Karadimou, Alexandra; Zucman‐Rossi, Jessica; Debruyne, Philip R.; Poppel, Hendrik Van; Joniau, Steven; Lerut, Evelyne; Strijbos, Michiel; Dumez, Herlinde; Paridaens, Robert; Calster, Ben Van; Schöffski, Patrick

doi:10.1111/bju.12494

Cited by 70 publications

(51 citation statements)

References 39 publications

(45 reference statements)

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“…In this series, of the 7 significant predictors of OS identified by univariate analysis, the MSKCC classification, CRP level and liver metastasis were found to be independently correlated with OS. The prognostic significance of these parameters has already been reported in several previous studies (11,(13)(14)(15)(16)(17). The common findings regarding prognostic indicators across various studies suggest the significant effect of the underlying biology of mRCC on disease control, even in the era of molecular-targeted therapy.…”

Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 61%

Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan

Miyazaki

Harada

Inoue

et al. 2015

Molecular and Clinical Oncology

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Abstract. The aim of this study was to evaluate the oncological efficacy of tyrosine kinase inhibitors (TKIs) as first-line molecular-targeted therapy for Japanese patients with metastatic renal cell carcinoma (mRCC) in a routine clinical setting. This study included a total of 271 consecutive Japanese patients with TKI-naive mRCC, including 172 patients who received sorafenib and 99 who received sunitinib for ≥2 months as a first-line molecular-targeted agent. The prognostic outcomes of these patients were retrospectively assessed. During the observation period (median, 19 months), 126 patients (46.5%) succumbed to the disease and the median overall survival (OS) for the entire cohort was 33.1 months. The univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, histological subtype and sarcomatoid characteristics as significant predictors of OS. Of these factors, only the MSKCC classification, CRP level and liver metastasis were found to be independently associated with OS in the multivariate analysis. Furthermore, there were significant differences in OS according to the positivity for these 3 independent risk factors (i.e., negative for all factors vs. positive for a single factor vs. positive for 2 or 3 factors). These findings suggest that the introduction of TKIs as first-line molecular-targeted agents resulted in favorable cancer control outcomes in Japanese mRCC patients and that the prognosis of these patients may be stratified by 3 potential parameters, including the MSKCC classification, CRP level and liver metastasis.

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Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 61%

Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan

Miyazaki

Harada

Inoue

et al. 2015

Molecular and Clinical Oncology

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“…The IMDC and MSKCC prognostic scores were calculated at start of second-line therapy, as well as the different factors that form the basis for these established scores (interval between diagnosis and systemic treatment, performance status, hemoglobin levels, corrected serum calcium levels, serum LDH levels, neutrophil and platelet count), presence of sarcomatoid dedifferentiation in 25% of the tumor volume [12], PFS [13] and best response on first-line therapy, the presence of bone metastases [14], brain metastases [15] or glandular metastases (defined as pancreatic, adrenal or thyroid metastases) [16], baseline C-reactive protein (CRP) levels ( or4inferior limit of normal, 5 mg/dl) [17] and albumin levels ( or4inferior limit of normal, 3.5 g/dl) [18,19] at start of second-line therapy. Associations between PFS or OS and potential prognostic factors were assessed using Kaplan-Meier estimates and the logrank test in univariate analysis.…”

Section: Methodsmentioning

confidence: 99%

Prognostic factors in second-line targeted therapy for metastatic clear-cell renal cell carcinoma after progression on an anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor

Sacré

Barthélémy²,

Korenbaum³

et al. 2015

Acta Oncologica

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Submit your article to this journal Background: About 40% of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients receive a second-line targeted therapy after failure of anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKI). Efficacy of second-line therapy is usually limited and prognostic and predictive factors at the start of second-line therapy are lacking. To identify the subgroup of patients that will benefit from such treatment remains a challenge. Methods: We performed a multi-institutional, retrospective study of patients who received a second-line therapy after progression on an anti-VEGFR-TKI. Univariate and multivariate analyses were performed in order to identify prognostic factors for progressive disease (PD) as best response, progression-free survival (PFS) and overall survival (OS) on second-line therapy. Results: For the whole cohort of 108 patients, mOS from the start of second-line therapy was 8.9 months while mPFS on second-line therapy was 2.8 months. A total of 49/105 (47%) patients had PD, 50/105 (48%) stable disease (SD) and 6/105 (6%) a partial response (PR). On multivariate analysis, the following markers were associated with improved outcome on second-line therapy: a PFS on first-line therapy 12 months (HR for PFS: 1.961; p ¼ 0.008) (HR for OS: 1.724; p ¼ 0.037) and Fuhrman grade 1-2 tumors (HR for OS: 2.198; p ¼ 0.007). Markers associated with poorer outcome on second-line therapy were: elevated serum lactate dehydrogenase (LDH) levels (HR for PFS: 0.511; p ¼ 0.04) (HR for OS: 0.392; p ¼ 0.017), low albumin (HR for OS: 0.392; p ¼ 0.01) and elevated corrected calcium levels (HR for OS: 0.416; p ¼ 0.01). The impact on OS of the Memorial Sloan Kettering Cancer Centre (MSKCC) and International Renal Cell Carcinoma Database Consortium (IMDC) prognostic scores as calculated at start of second-line therapy was validated in our patient series. Conclusions: Duration of first-line PFS, Fuhrman grade, serum LDH levels, albumin levels, corrected calcium levels and the MSKCC and IMDC scores calculated at start of second-line therapy are prognostic factors for m-ccRCC patients treated with second-line targeted therapy.

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“…CRP has been shown to be a non-specific biomarker in patients with various stages of RCC who receive surgery (13-16,18-21), immunotherapy (13,15,17,22,23) and molecular-targeted therapy (9)(10)(11)(12). CRP has a promising role in predicting survival among patients with localized and metastatic RCC.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have revealed a prognostic role for CRP in the outcome of sunitinib treatment (9)(10)(11)(12). Normal pretreatment CRP levels predict a higher response rate and better survival among patients undergoing sunitinib treatment (9,11).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic effect of serum C-reactive protein kinetics on advanced renal cell carcinoma treated with sunitinib

Fujita

Tabata

Ishii

et al. 2017

Molecular and Clinical Oncology

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Abstract. C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the prognostic effect of pretreatment serum CRP level and CRP kinetics on patients with advanced RCC treated with sunitinib. A total of 56 consecutive patients with advanced RCC treated with sunitinib between December, 2008 and December, 2012 were enrolled in the present study. The patients were retrospectively divided into 3 cohorts according to pretreatment serum CRP level and CRP kinetics: i) Normal CRP cohort (pretreatment CRP ≤0.30 mg/dl); ii) normalized CRP cohort (pretreatment CRP >0.30 mg/dl that normalized within 2 cycles of treatment); and iii) non-normalized CRP cohort (pretreatment CRP >0.30 mg/dl that did not normalize after sunitinib initiation). Disease control rate, progression-free survival and overall survival times were compared for the 3 cohorts. The normal (n=17, 30.4%) and the normalized (n=8, 14.3%) CRP cohorts exhibited significantly better disease control rates compared with the non-normalized CRP cohort (n=31, 55.4%; P<0.0001 and P=0.0445, respectively). The normal CRP cohort exhibited significantly longer progression-free survival compared with the non-normalized CRP cohort (P=0.0050). The normal and normalized CRP cohorts exhibited significantly longer overall survival compared with the non-normalized CRP cohort (P=0.0005 and 0.0466, respectively). Therefore, CRP kinetics and normal pretreatment CRP level are prognostic indicators in patients with advanced RCC treated with sunitinib. IntroductionC-reactive protein (CRP), which was found to be a representative acute-phase reactant in 1930, is the most widely used marker of systemic inflammation (1). Inflammation plays an important role during almost all stages of tumor development (2). For example, the proliferation of renal cell carcinoma (RCC) is associated with increased levels of interleukin-6 (IL-6), nuclear factor-κB, and other inflammatory factors (3,4), and the serum CRP levels were found to be correlated with the levels of proinflammatory cytokines, such as IL-6 (5). Numerous studies have demonstrated that CRP is a significant prognostic factor among patients with RCC at various stages, whether they are being treated by surgery, systemic therapy, or both (6).Sunitinib malate (Sutent, Pfizer Inc., New York, NY, USA) is an orally administered, small-molecule, multitargeted inhibitor of tyrosine kinases (e.g., vascular endothelial growth factor receptor, platelet-derived growth factor receptor, phosphorylation of stem cell factor receptor, Fms-like tyrosine kinase-3, colony-stimulating factor-1 receptor, and RET receptor tyrosine kinases). In a phase III clinical trial including patients with advanced RCC, sunitinib achieved significantly better results compared with interferon (IFN)-α and is approved worldwide for the treatment of advanced RCC (7,8). The number of patients treated with sunitinib is increasing and, therefore, there is an urgent need to identify biomarkers that may...

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Prognostic impact of baseline serum C‐reactive protein in patients with metastatic renal cell carcinoma (RCC) treated with sunitinib

Cited by 70 publications

References 39 publications

Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan

Prognostic outcome in patients treated with tyrosine kinase inhibitors as first-line molecular-targeted therapy for metastatic renal cell carcinoma: Experience in real-world clinical practice in Japan

Prognostic factors in second-line targeted therapy for metastatic clear-cell renal cell carcinoma after progression on an anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor

Prognostic effect of serum C-reactive protein kinetics on advanced renal cell carcinoma treated with sunitinib

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