Clinical outcomes according to ethnicity in patients with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16065-e16065
Author(s):  
Dominick Bosse ◽  
Wanling Xie ◽  
Connor Wells ◽  
Aly-Khan A. Lalani ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Risk Groups ◽  
Eligibility Criteria ◽  
Best Response ◽  
Metastatic Sites

e16065 Background: Discrepancies in clinical outcomes between different ethnic groups are well known in cancer patients. Differences in mRCC patients receiving VEGF-TT are less well characterized. We thought to report on baseline characteristics and treatment outcomes in African-Americans (AA) and Hispanic patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Methods: Caucasians, AA and Hispanics with mRCC treated with 1stline VEGF-TT were identified from the IMDC. We created 2 matched cohorts: 1) AA vs. Caucasians and 2) Hispanics vs. Caucasians, both matched for age (<50; 50-59; 60-69; <70-year-old), gender, years of treatment (2003-07; 2008-12; 2013-16) and geography (Canada, USA, Europe). Weighted Cox and logistic regressions were used to compare OS, time-to-treatment failure (TTF) and best response, adjusted for nephrectomy status, IMDC risk groups, number of metastatic sites (1 v. >1) and histology (clear-cell vs. else). Results: 73 AA and 71 Hispanics met eligibility criteria and were matched with 1236 and 901 eligible Caucasians, respectively. AA had more non-clear cell histology (26% v. 11%), time from diagnosis to therapy<1 year (67% v. 55%) and anemia (75% v. 54%) vs. Caucasians. Differences were not significant for Hispanics. Clinical outcomes are presented in Table. Conclusions: Adjusted for clinical prognostic factors, Hispanics with mRCC have statistically shorter TTF and survival than Caucasians. AA had a trend toward shorter TTF (not significant) but similar survival than Caucasians. Underlying genetic/biological differences, along with potential cultural variations, may impact survival in Hispanic mRCC patients. [Table: see text]

scholarly journals The clinical significance of routine risk categorization in metastatic renal cell carcinoma and its impact on treatment decision-making: a systematic review

2020 ◽  
Vol 16 (34) ◽  
pp. 2879-2896
Author(s):  
Shouki Bazarbashi ◽  
Abdullah Alsharm ◽  
Faisal Azam ◽  
Hazem El Ashry ◽  
Jamal Zekri
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Cancer Center ◽  
Eligibility Criteria

Aim: To analyze responses to first-line metastatic renal cell carcinoma (mRCC) treatment stratified by risk criteria. Patients & methods: Clinical trials and observational studies of patients aged ≥18 years, published January 2005–May 2019, were identified via Ovid from MEDLINE, EMBASE, the Cochrane Central Trials Register and the Cochrane Database of Systematic Reviews. Data extracted included progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Results: 47/1269 articles met eligibility criteria. Most studies stratified patients by International Metastatic RCC Database Consortium (n = 19) or Memorial Sloan Kettering Cancer Center (n = 21). PFS, OS and ORR varied according to risk group. Conclusion: Pembrolizumab + axitinib, ipilimumab + nivolumab and avelumab + axitinib were most effective across all risk groups. Favorable-risk patients benefit from sunitinib treatment.

Association of PD-1 and PD-L1 protein expression in matched primary and metastatic renal cell carcinoma tumors.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 418-418 ◽  
Author(s):  
Brian I. Rini ◽  
Jennifer Yearly ◽  
Hari Dhakal ◽  
Christopher Przybycin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Linear Regression Analysis ◽  
Matched Pair ◽  
Primary Tumors ◽  
Metastatic Site ◽  
Metastatic Sites

418 Background: Therapy targeting programmed death (PD)-1 and PD-L1 proteins has activity in metastatic renal cell carcinoma (mRCC). Expression of these proteins on tumor and infiltrating immune cells is associated with a higher response to drugs inhibiting this pathway. However, these associations have been made based on primary tumor expression, while therapy is directed against metastatic deposits. Methods: Patients with mRCC and metastases (all clear cell; 3 with sarcomatoid changes) who had undergone resection of both the primary and at least one metastatic tumor were included. Samples were evaluated for PD-1 and PD-L1 expression by immunohistochemistry using anti-PD-1 clone NAT105 and Merck proprietary anti-PD-L1 clone 22C3. Stained sections were scored for PD-1 and PD-L1 using a semi-quantitative 0 to 5 scale (0 = negative, 1 = rare, 2 = low, 3 = moderate, 4= high, 5 = very high). PD-1 expression was limited to cells with lymphoid morphology, PD-L1 expression was evaluated for both tumor and non-tumor (inflammatory, endothelial) cells. Linear regression analysis was performed to assess significance of correlations. Results: Fifty matched primary and metastatic RCC tissue sets were analyzed with 48 evaluable matched pairs. PD-1 score greater than 3 (considered positive) was detected in 9 primary tumors (18%) and 9 metastatic sites (18%). PD-L1 score greater than 3 was detected in 9 primary tumors (18%) and 12 metastatic sites (24%). There was a correlation between PD-1 scores for primary and metastatic pairs (R2=0.194; p<0.002) and between PD-L1 scores for primary and metastatic pairs (R2=0.319; p<0.0001). There was an association between PD-1 score and PD-L1 score for primary tumors (R2=0.513; p<0.0001) and for metastatic sites (R2=0.449; p<0.0001). For PD-1 score, there were 10 pairs (21%) in which either the primary or metastatic site score was ≥3, but the matched pair was < 3. For PD-L1 score, there were 9 pairs (19%) in which either the primary or metastatic site score was ≥3, but the matched pair was < 3. Conclusions: The expression of PD1 and PD-L1 in primary clear cell RCC tumors is correlated with metastatic site expression, although there are a substantial percentage of tumors with discordance.

scholarly journals Racial Differences in Clinical Outcomes for Metastatic Renal Cell Carcinoma Patients Treated With Immune-Checkpoint Blockade

2021 ◽  
Vol 11 ◽  
Author(s):  
T. Anders Olsen ◽  
Dylan J. Martini ◽  
Subir Goyal ◽  
Yuan Liu ◽  
Sean T. Evans ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Clear Cell ◽  
Caucasian Patients ◽  
Clear Cell Rcc

BackgroundImmune-checkpoint-inhibitors (ICIs) have become the cornerstone of metastatic renal-cell-carcinoma (mRCC) therapy. However, data are limited regarding clinical outcomes by race. In this study, we compared the real-world outcomes between African American (AA) and Caucasian mRCC patients treated with ICIs.MethodsWe performed a retrospective study of 198 patients with mRCC who received ICI at the Emory Winship Cancer Institute from 2015-2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) defined as a complete or partial response maintained for at least 6 months per response evaluation criteria in solid tumors version 1.1. Univariate and multivariable analyses were carried out for OS and PFS by Cox proportional-hazard model and ORR by logistical-regression model. Descriptive statistics compared rates of immune-related adverse events (irAEs) and non-clear-cell-RCC (nccRCC) histology were assessed using Chi-square test.ResultsOur cohort was comprised of 38 AA and 160 Caucasian patients. Most were diagnosed with clear-cell-RCC (ccRCC) (78%) and more than half received (57%) PD-1/PD-L1 monotherapy. Most patients were intermediate or poor-risk groups (83%). Comparing to Caucasians, our AA cohort contained more females and nccRCC cases. Kaplan-Meier method showed AAs had no statistically different median OS (17 vs 25 months, p=0.368) and PFS (3.1 vs 4.4 months, p=0.068) relative to Caucasian patients. On multivariable analysis, AA patients had significantly shorter PFS (HR=1.52, 95% CI: 1.01-2.3, p=0.045), similar ORR (OR=1.04, 95% CI: 0.42-2.57, p=0.936) and comparable OS (HR=1.09, 95% CI: 0.61-1.95, p=0.778) relative to Caucasians.ConclusionsOur real-world analysis of ICI-treated mRCC patients showed that AAs experienced shorter PFS but similar OS relative to Caucasians. This similarity in survival outcomes is reassuring for the use of ICI amongst real-world patient populations, however, the difference in treatment response is poorly represented in early outcomes data from clinical trials. Thus, the literature requires larger prospective studies to validate these findings.

scholarly journals Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers

BMC Cancer ◽  
2009 ◽  
Vol 9 (1) ◽  
Author(s):  
Loukas F Kontovinis ◽  
Konstantinos T Papazisis ◽  
Panagiota Touplikioti ◽  
Charalambos Andreadis ◽  
Despoina Mouratidou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Sunitinib Treatment

223 Racial differences in outcomes for metastatic renal cell carcinoma (mRCC) patients managed on immune-checkpoint inhibitor (ICI) therapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A242-A242
Author(s):  
T Anders Olsen ◽  
Dylan Martini ◽  
Subir Goyal ◽  
Yuan Liu ◽  
Sean Evans ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
African American ◽  
Retrospective Study ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Clear Cell ◽  
Emory University ◽  
Caucasian Patients

BackgroundImmune checkpoint inhibitors (ICIs) have increased in prevalence for the treatment of metastatic clear-cell renal cell carcinoma (mccRCC) in recent years given their efficacy and favorable toxicity profile. However, there has been insufficient investigation in the literature of how clinical outcomes differ on the basis of race. In this paper, we investigated differences in clinical outcomes between African American (AA) and Caucasian mRCC patients treated with ICI therapy.MethodsWe performed a retrospective study of 198 patients with mRCC who received ICI at the Emory Winship Cancer Institute from 2015–2020. Clinical outcomes were measured by overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from ICI-initiation to date of death and radiographic or clinical progression, respectively. CB was defined as a best radiographic response of complete response, partial response, or stable disease maintained for at least 6 months per response evaluation criteria in solid tumors version 1.1. The association of self-identified race with OS and PFS was generally modeled by Cox proportional hazards model. Univariable and multivariable logistic regression models were used for binary outcomes of CB. The univariate association of immune-related adverse events (irAEs) and non-clear-cell RCC (nccRCC) with race was assessed using Chi-square test.ResultsOur cohort was made up of 38 AA (19%) and 160 Caucasian (81%) patients. Most of the patients were diagnosed with ccRCC (78%) and more than half received PD-1 monotherapy (57%). Most patients were international mRCC database consortium (IMDC) intermediate (57%) or poor-risk (25%) groups. AA patients displayed significantly shorter PFS (HR=1.52, 95% CI: 1.01–2.3, p=0.045) and trended towards decreased CB (OR=0.51, 95% CI: 0.22–1.17, p=0.111) in MVA (table 1). There was no difference in OS (HR=1.09, 95% CI: 0.61–1.95, p=0.778) between the two racial groups in MVA (table 1). On Kaplan-Meier method, AA patients had shorter median OS (17 vs 25 months, p=0.3676) and median PFS (3.1 vs 4.4 months, p=0.0676) relative to Caucasian patients (figure 1). Additionally, AA patients more commonly had nccRCC compared to Caucasian patients (41.7% vs 17.5% nccRCC, p-0.002). AA patients also trended towards a lower incidence of irAEs compared to Caucasian patients in UVA (23.7% vs 35.8%, p=0.153).Abstract 223 Table 1*MVA controlled for age, race, gender, IMDC risk group, number of prior lines of therapy, PD-1 monotherapy, and ccRCC**statistical significance at alpha < 0.05Abstract 223 Figure 1African-American (black) and Caucasian (white) for OS (left panel) and PFS (right panel)ConclusionsIn this group of mRCC patients treated with ICI, African American patients had significantly shorter PFS compared to Caucasian patients. These findings suggest race could play a role in the management of late-stage mRCC. Larger, prospective studies are needed to validate these findings.AcknowledgementsResearch reported in this publication was supported in part by the Breen Foundation and the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Trial RegistrationNot applicable.Ethics ApprovalThis retrospective study was approved by the Emory University Institutional Review Board.ConsentNot applicable.ReferencesNot applicable

scholarly journals MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Brian Shuch ◽  
Ryan Falbo ◽  
Fabio Parisi ◽  
Adebowale Adeniran ◽  
Yuval Kluger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarkers ◽  
Cell Renal Cell Carcinoma ◽  
Primary Tumors ◽  
Distant Tissue ◽  
Significant Expression ◽  
Metastatic Sites

Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available.Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1). MET expression weakly correlated between primary and matched metastatic sites (R=0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39).Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

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