MP69-08 SYSTEMATIC REVIEW AND META-ANALYSIS OF TARGETED THERAPY FOR OVERALL SURVIVAL, COMPLETE RESPONSE AND QUALITY OF LIFE FOR METASTATIC RENAL CELL CARCINOMA

468 Background: The cell-based therapeutic cancer vaccine MGN1601 consists of two active pharmaceutical ingredients in fixed combination. Fourfold gene-modified, allogeneic tumor cells expressing IL-7, GM-CSF, CD80, and CD154 through MIDGE gene expression vectors are combined with the DNA-based immunomodulator dSLIMas a TLR-9 agonist. In the phase I-II clinical trial (ASET trial) heavily pre-treated patients with metastatic renal cell carcinoma (mRCC) were enrolled. Methods: TheASET study has been conducted as a multicenter, open, single-arm phase I-II study. The treatment phase (TP) consisted of 8 intradermal vaccinations, administered within 12 weeks. We analysed known mRCC prognostic factors for their predictive value, i.e. safety laboratory and immunological parameters, quality of life, local reactions and other patients’ characteristics. Results: 19 patients from the ASET study, who received at least one vaccination (ITT population), were included in the biomarker evaluation. The median overall survival (mOS) in the ITT population is currently 25 weeks. mOS of patients who discontinued TP prematurely was only 10 weeks. However, mOS of those patients who completed at least TP is not yet mature for statistical calculation (NR), but is currently estimated as 69 weeks, resulting in a highly significant difference (10 weeks vs. NR, p < 0.001). Patients with an absolute lymphocyte counts (ALC) at baseline of ≥1,000/μL had increased overall survival (mOS NR vs. 16 weeks, p = 0.013), if compared to those with an ALC <1,000/μL. Neutrophil lymphocyte ratios (NLR) at baseline of >3, bone and liver metastasis, high MSKCC score were identified as risk factors associated with lower overall survival. ALC ≥1,000/μL after three MGN1601 vaccinations (week 5) was even more significantly associated with increased overall survival (mOS NR vs. 17 weeks, p = 0.007). The NLR and quality of life improvement at week 5 as well as local reactions at injection sites seem to correlate with OS. Conclusions: MGN1601 shows promising efficacy in late stage mRCC patients. The identified parameters should be further investigated as potential biomarkers for efficacy. Clinical trial information: NCT01265368.

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Efficacy of adjuvant vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (VEGFRi) in renal cell carcinoma (RCC): A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.680 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 680-680

Author(s):

Tobias Engel Ayer Botrel ◽

Otávio Clark ◽

Francisco Flávio Horta Bretas ◽

Marcus V. Sadi ◽

Ubirajara Ferreira ◽

...

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Meta Analysis ◽

Locally Advanced ◽

Disease Free Survival ◽

Fixed Effect

680 Background: To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing the efficacy of adjuvant VEGFRi in locally advanced, non-metastatic clear renal-cell carcinoma (RCC). Methods:Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. We included studies that compared the addition of VEGFRi versus placebo, after nephrectomy. Analyzed endpoints were overall survival (OS) and disease-free survival (DFS). The data extracted from the studies were combined by using Hazard Ratio (HR) or Risk Ratio (RR) with their corresponding Confidence Intervals of 95% (CI95%). Results: Overall, 121 references were identified and screened. The final analysis included 5 trials (S-TRAC, ATLAS, ASSURE, PROTECT and SORCE) comprising 6,128 patients that underwent previous nephrectomy for RCC. The DFS was similar in patients who received VEGFRi (fixed effect: HR=0.94, CI95%=0.87 to 1.03; p=0.19), with no heterogeneity (Chi2 = 4.33, df = 5 (P=0.50); I2 = 0%). Overall survival also was not statistically better in patients who received VEGFR inhibitors (HR=1.01, CI95%=0.90 to 1.15; p=0.84), with no heterogeneity (Chi2= 3.57, df = 5 (P=0.61); I2 = 0%). In the final combined analysis of the higher-risk disease group (pT3, pT4, or N+ disease), patients who received VEGFRi had a longer DFS (fixed effect: HR=0.85, CI95%=0.74 to 0.97; p=0.02), with no heterogeneity (Chi2 = 2.46, df = 3 (P=0.48); I2 = 0%). Overall survival was not statistically different for these higher-risk disease patients (fixed effect: HR=0.93, CI95%=0.74 to 1.16; p=0.5). Conclusions: This is the first meta-analysis including the five available RCTs in the literature (the previous meta-analysis reviewed only four), comparing adjuvant VEGFRi versus placebo in patients submitted to nephrectomy with a locally advanced, non-metastatic RCC. Adjuvant VEGFRi did not increase the OS in this group of patients. Amodest benefit of DFS with the use of adjuvant VEGFR inhibitors was restricted to patients with the highest risk of relapse.

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Capabilities of preoperative targeted therapy in treatment of bone metastases in renal cancer

Cancer Urology ◽

10.17650/1726-9776-2019-15-2-35-41 ◽

2019 ◽

Vol 15 (2) ◽

pp. 35-41

Author(s):

Z. A. Yurmazov ◽

N. A. Lushnikova ◽

L. V. Spirina ◽

E. A. Usynin ◽

E. M. Slonimskaya ◽

...

Keyword(s):

Quality Of Life ◽

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Surgical Treatment ◽

Bone Metastases ◽

Cell Carcinoma ◽

Renal Cell ◽

Study Objective ◽

Bone Segment

The study objective is to evaluate the effectiveness of preoperative targeted therapy, spectrum and rate of adverse events, as well as quality of life in patients with bone metastases of renal cell carcinoma.Materials and methods. The study was conducted at the Research Institute of Oncology, Tomsk Medical Research Center between 2014 and 2018. The study included 34 patients with bone metastases of renal cell carcinoma who received preoperative targeted therapy with pazopanib for 8 weeks. All patients underwent surgical treatment of both the primary tumor and bone metastases.Results and conclusion. It was shown that preoperative targeted therapy is characterized by a high rate of clinical response and satisfactory tolerability. In some cases, preoperative targeted therapy improves the conditions for surgical treatment of metastatic bone lesions, decreases intraoperative blood loss, decreases the volume and duration of surgical intervention, which, in turn, allows to preserve bigger range of motion in the affected bone segment and improve patients’ quality of life.

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Quality of life (QoL) and overall survival (OS) in patients (pts) with advanced clear-cell renal cell carcinoma (aRCC) treated with nivolumab (NIVI) vs. everolimus (EVE) in the phase III CheckMate 025 study.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.4549 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. 4549-4549 ◽

Cited By ~ 1

Author(s):

David Cella ◽

Viktor Gruenwald ◽

Paul D. Nathan ◽

Justin Doan ◽

Homa Dastani ◽

...

Keyword(s):

Quality Of Life ◽

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Phase Iii ◽

Cell Renal Cell Carcinoma

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Adjuvant targeted therapy combined with surgery for advanced and metastatic renal cell carcinoma: Protocol for a systematic review and meta-analysis

10.37766/inplasy2020.11.0093 ◽

2020 ◽

Author(s):

Hongyu Jin ◽

Man Zhang

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Meta Analysis

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Quality of life and complications after nephron-sparing treatment of renal cell carcinoma stage T1—a systematic review

Systematic Reviews ◽

10.1186/s13643-021-01868-2 ◽

2022 ◽

Vol 11 (1) ◽

Author(s):

Theresa Junker ◽

Louise Duus ◽

Benjamin S. B. Rasmussen ◽

Nessn Azawi ◽

Lars Lund ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Partial Nephrectomy ◽

Complication Rate ◽

Renal Cell ◽

Nephron Sparing ◽

Stage T1

Abstract Background Despite the fact that nephron-sparing treatment is considered preferable from a surgical perspective patients’ quality of life (QoL) following different types of nephron-sparing treatments remains unclear. Purpose To investigate the quality of life and complications after nephron-sparing treatment of renal cell carcinomas of stage T1. Materials and methods A systematic search of six databases was carried out. We included studies that reported the quality of life and complications in patients aged 18 years or older following nephron-sparing treatment of renal cell carcinoma stage T1. The quality assessment was performed using the Critical Appraisal Skills Programme (CASP) checklist for cohort studies and the CASP Randomized Controlled Trial Checklist. Data were analyzed using a narrative approach. Results Eight studies were included, six of which investigated QoL after partial nephrectomy and two after ablation therapies. Seven studies reported complications. Three studies reported higher QoL scores after partial nephrectomy compared to radical nephrectomy. Two studies showed that QoL increased or returned to baseline levels up to 12 months following partial nephrectomy. One study reported a gradual increase in QoL after radiofrequency ablation, and one study reported that all patients recovered to baseline QoL following cryoablation. Across studies, we found a complication rate up to 20% after partial nephrectomy and up to 12.5% after ablation therapy. Conclusions The results of this systematic review suggest that nephron-sparing treatment appears to be superior or comparable to other treatment alternatives with regard to QoL outcomes. Additionally, based on the studies included in this review, partial nephrectomy appears to have a higher complication rate compared with ablation therapies. Systematic review registration PROSPERO CRD42020155594

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