Therapy For Metastatic Renal Carcinoma Research Articles

827P - Clinical outcomes and dosing patterns of 2nd targeted therapy in metastatic renal carcinoma: a retrospective chart review in the EU

This study evaluates the real-world outcomes and dosing patterns of metastatic renal cell carcinoma (mRCC) patients treated with everolimus (EVE), axitinib (AXI), and sorafenib (SOR), and as 2nd targeted therapy in Europe. We expanded the study to include patients from an additional country and updated the results presented at ASCO GU 2016 (#558). Oncologists and urologists in the UK, Germany, France, and the Netherlands reviewed charts of adult mRCC patients who experienced disease progression on 1st targeted therapy with sunitinib or pazopanib and initiated 2nd targeted therapy with EVE, AXI, or SOR between 10/2012 and 6/2013. Overall survival (OS) and progression-free survival (PFS) and from the initiation of 2nd targeted therapies were evaluated using Kaplan-Meier analyses, and compared across cohorts using multivariable Cox proportional hazards models. Proportions of patients with dose adjustments and dose intensities relative to the recommended doses were also compared. A total of 309 charts were reviewed, with 115, 96, and 98 mRCC patients receiving EVE, AXI, and SOR as 2nd targeted therapy, respectively. Mean age was 60.2 years and 66.7% were male. The majority of patients received sunitinib as 1st targeted therapy (79.3%) and the rest received pazopanib (20.7%). No statistically significant differences were observed in OS or PFS after adjusting for patient characteristics [AXI vs. EVE: hazard ratio (HR) (95% CI): 1.22 (0.77-1.94) and 1.26 (0.81-1.95); SOR vs. EVE: HR (95% CI): 1.25 (0.75-2.10) and 1.47 (0.95-2.28)]. A significantly greater proportion of AXI-treated patients had a dose increase (AXI: 13.2% vs. EVE: 0.9%, p < 0.01; vs. SOR: 0.0%, p < 0.01). Relative dose intensity was also significantly higher in AXI-treated patients (AXI: 1.02 vs. EVE: 0.91, p < 0.01; vs. SOR: 0.88, p < 0.01). In this retrospective study, no statistically significant differences in OS or PFS were observed among patients treated with EVE, AXI, and SOR. Rates of dose escalation and relative dose intensities were significantly higher among AXI-treated patients compared to EVE- or SOR-treated patients.

Outcomes of second targeted therapy in metastatic renal carcinoma: A retrospective chart review in the EU.

558 Background: This study describes the real-world outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus (EVE), sorafenib (SOR), and axitinib (AXI) as 2nd targeted therapy in the UK, Germany, and France. Methods: A retrospective chart review was conducted among oncologists and urologists in the UK, Germany and France. Charts were reviewed for adult mRCC patients satisfying the following eligibility criteria: 1) experienced disease progression on 1st targeted therapy with sunitinib or pazopanib; 2) initiated 2nd targeted therapy with EVE, AXI, or SOR between 10/2012 and 6/2013. Kaplan-Meier analysis was used to estimate overall survival (OS) after initiation of 2nd targeted therapy among all patients and stratified by type of 2nd targeted therapy. Results: A total of 281 charts were reviewed, with 99, 91, and 91 mRCC patients receiving EVE, AXI, and SOR as 2nd targeted therapy, respectively. Mean age was 60.6 years old at initial mRCC diagnosis and 65.5% were male. The majority of patients used sunitinib (79.4%), with the rest using pazopanib (20.6%) as 1st targeted therapy. Median duration of 1st targeted therapy was 9.7 months. At the initiation of 2nd targeted therapy, 91.8% of patients had an ECOG score ≤ 2. The most common sites of metastases were lung (71.2%), bone (53.0%), and lymph nodes (47.0%). Median OS from the initiation of 2nd targeted therapy among all patients was 21.8 months (95% CI: 16.5-26.2). The median OS was 23.0, 23.5, and 18.7 for EVE, AXI, and SOR respectively. The majority of patients (87.5%) initiated 2nd targeted therapy on the recommended dose. Patients receiving AXI had a higher rate of dose increase (13.2%), compared to EVE (1.0%) and SOR (0.0%), while patients on EVE had a higher rate of dose decrease (12.1%), compared to AXI (5.5%) and SOR (8.8%). Conclusions: In this retrospective chart review study of several EU countries, the observed median OS was numerically comparable for EVE and AXI, but rates of dose adjustment differed by treatments. Retrospective chart reviews may be subject to selection bias and errors in data entry, and further analysis is underway to address confounding effects of unobserved patient characteristics.

Targeted Therapy for Metastatic Renal Carcinoma: an Update

Conventional chemotherapy is associated with poor outcomes in metastatic renal cell carcinoma (RCC). Advances in the understanding of tumor molecular biology and the implementation of new drugs that target these molecular pathways have increased the arsenal against advanced RCC and improved outcomes in these patients. Herein, we briefly describe the latest data on targeted therapies used in the treatment of advanced renal cell carcinoma. Search strategy was performed according to PRISMA guidelines. s of relevant studies published in PubMed between 2000 and 2014 were analyzed by two authors. s were selected if they were published in English, data reported was of phase II or III clinical trials, and outcomes followed FDA approval. If consensus between the two authors was achieved, they were included in the review. Key words used were “target therapy” and “metastatic renal cell carcinoma”. The results of the studies analyzed in this review support the benefits of targeted therapy in metastatic RCC. These include improved progression-free survival, overall survival, and quality of life as well as reduced toxicities compared to immunotherapy. The improvement in outcomes in metastatic RCC makes these drugs a preferred option as a primary treatment for these patients.

Targeted therapy in metastatic renal carcinoma

BackgroundAdvanced renal cell carcinoma is one of the most treatment-resistant malignancies to conventional cytotoxic chemotherapy. The development of new targeted therapy was result of understanding biological pathways underlying renal cell carcinoma. Our objective is to provide an overview of current therapies in metastatic renal cell carcinoma. MethodsMEDLINE/PUBMED was queried in December 2012 to identify abstracts, original and review articles. The research was conducted using the following words: “metastatic renal cell carcinoma” and “target therapy”. Phase II and Phase III clinical trials were included followed FDA approval. Total of 40 studies were eligible for review. ConclusionThe result of this review shows benefit of these target drugs in tumor burden, increase progression-free and overall survival and improvement the quality of life compared with previous toxic immunotherapy, although complete response remains rare.

176 In vitro human metabolism of BAY 57-9352: a novel VEGFR-2/PDGFR kinase inhibitor

Objectives. To determine whether the tumor-associated neovasculature of metastatic prostate and metastatic conventional (clear cell) renal carcinoma express prostate-specific membrane antigen (PSMA). PSMA is a type II integral membrane glycoprotein highly expressed in prostate cancer cells and also recently discovered to be expressed in the neovasculature of non-prostatic primary malignancies.Methods. We examined metastatic prostate carcinoma (22 patients) and metastatic conventional (clear cell) renal carcinoma (20 patients) in various anatomic sites, including bone, lymph nodes, liver, lung, and soft tissue. Using the biotin-streptavidin method, we performed immunohistochemical reactions with the anti-PSMA monoclonal antibodies (mAbs) 7E11 and PM2J004.5 and with the anti-endothelial cell mAb CD34.Results. Metastatic conventional (clear cell) renal carcinoma consistently expressed PSMA. The PM2J004.5 mAb was positive in 20 of 20 specimens, and the 7E11 mAb was positive in 15 of 20. The anti-PSMA immunoreactions with the neovasculature were confirmed by similar staining by the anti-CD34 mAb (20 of 20). Although the metastatic prostatic cancer cells expressed PSMA in all the specimens, only 2 of 22 had neovasculature PSMA expression.Conclusions. As in primary prostatic adenocarcinomas, the neovasculature of metastatic prostate cancer, regardless of site, rarely express PSMA. The neovascular endothelial cells of metastatic clear cell renal carcinoma, however, express PSMA. This expression may make PSMA an effective target for mAb-based antineovasculature therapy in metastatic renal carcinoma.

Metastatic renal cell carcinoma neovasculature expresses prostate-specific membrane antigen

Objectives. To determine whether the tumor-associated neovasculature of metastatic prostate and metastatic conventional (clear cell) renal carcinoma express prostate-specific membrane antigen (PSMA). PSMA is a type II integral membrane glycoprotein highly expressed in prostate cancer cells and also recently discovered to be expressed in the neovasculature of non-prostatic primary malignancies. Methods. We examined metastatic prostate carcinoma (22 patients) and metastatic conventional (clear cell) renal carcinoma (20 patients) in various anatomic sites, including bone, lymph nodes, liver, lung, and soft tissue. Using the biotin-streptavidin method, we performed immunohistochemical reactions with the anti-PSMA monoclonal antibodies (mAbs) 7E11 and PM2J004.5 and with the anti-endothelial cell mAb CD34. Results. Metastatic conventional (clear cell) renal carcinoma consistently expressed PSMA. The PM2J004.5 mAb was positive in 20 of 20 specimens, and the 7E11 mAb was positive in 15 of 20. The anti-PSMA immunoreactions with the neovasculature were confirmed by similar staining by the anti-CD34 mAb (20 of 20). Although the metastatic prostatic cancer cells expressed PSMA in all the specimens, only 2 of 22 had neovasculature PSMA expression. Conclusions. As in primary prostatic adenocarcinomas, the neovasculature of metastatic prostate cancer, regardless of site, rarely express PSMA. The neovascular endothelial cells of metastatic clear cell renal carcinoma, however, express PSMA. This expression may make PSMA an effective target for mAb-based antineovasculature therapy in metastatic renal carcinoma.

Preparation of lymphocytes for autolymphocyte therapy in metastatic renal carcinoma

Preparation of lymphocytes for autolymphocyte therapy in metastatic renal carcinoma