scholarly journals Evaluation of disease-free survival as an intermediate metric of overall survival in patients with localized renal cell carcinoma: A trial-level meta-analysis

Cancer ◽  
2017 ◽  
Vol 124 (5) ◽  
pp. 925-933 ◽  
Author(s):  
Lauren C. Harshman ◽  
Wanling Xie ◽  
Raphael B. Moreira ◽  
Dominick Bossé ◽  
Gustavo J. Ruiz Ares ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Localized Renal Cell Carcinoma ◽  
Disease Free

Evaluation of disease-free survival as an intermediate metric for overall survival in localized renal cell carcinoma: A trial-level meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4585-4585 ◽  
Author(s):  
Lauren Christine Harshman ◽  
Wanling Xie ◽  
Raphael Brandao Moreira ◽  
Dominick Bosse ◽  
Gustavo Ruiz Ares ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Moderate Correlation ◽  
Free Survival ◽  
Localized Renal Cell Carcinoma ◽  
Disease Free

4585 Background: Adjuvant trials aim to integrate systemic therapy earlier to increase cure rates over surgery alone. Overall survival (OS) is a critical endpoint for these studies but requires long durations to events and significant patient resources. We explored the potential use of disease-free survival (DFS) as an intermediate readout for OS in the adjuvant setting for localized renal cell carcinoma (RCC). Methods: We performed a systematic literature review following the PRISMA guidelines. Inclusion criteria required randomized controlled trials (RCT) for adjuvant systemic therapy in localized RCC, which reported on both DFS and OS. Data on hazard ratio (HR) and 5-year event-free rate from Kaplan-Meier estimates were extracted. We performed a trial level meta-analysis and correlated these estimates for OS and DFS, weighted by the number of DFS events. R-square > 0.7 would indicate a strong correlation and potential for surrogacy. Results: Thirteen RCTs encompassing 6,473 patients treated with various forms of systemic therapy were eligible for the analyses. Minimum follow-up was 40 months. There was a moderate correlation between 5-year DFS and 5-year OS rates (R-square = 0.49, 95% CI:0.15-0.68) and between treatment effects as measured by DFS and OS hazard ratios (R-square = 0.44, 95% CI:0.00-0.69). Conclusions: Across trials of adjuvant systemic therapy for localized RCC, we observed a moderate correlation between 5-year DFS and OS rates and between treatment effects (HRs) on these endpoints. Further granularity may be achieved using individual patient data to assess different and earlier time points for surrogacy than are commonly reported. [Table: see text]

Randomized, double-blind phase III study of pazopanib versus placebo in patients with metastatic renal cell carcinoma who have no evidence of disease following metastasectomy: A trial of the ECOG-ACRIN cancer research group (E2810).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4502-4502 ◽  
Author(s):  
Leonard Joseph Appleman ◽  
Maneka Puligandla ◽  
Sumanta K. Pal ◽  
Wayne Harris ◽  
Neeraj Agarwal ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Patient Reported Outcomes ◽  
Disease Free Survival ◽  
Double Blind ◽  
Free Survival ◽  
Patient Reported ◽  
Disease Free

4502 Background: Patients with no evidence of disease (NED) after metastasectomy for metastatic renal cell carcinoma (mRCC) are at high risk of recurrence, but no systemic therapy has been shown to benefit this population. Pazopanib is an inhibitor of VEGFR and other kinases that improves progression-free survival in patients with measurable RCC metastatic disease. We performed a randomized, double-blind, placebo-controlled multicenter study to test the hypothesis that pazopanib would improve disease-free survival in patients with mRCC rendered NED after metastasectomy Methods: Patients with NED following metastasectomy were randomized 1:1 to receive pazopanib starting at 800 mg daily vs. placebo for 52 weeks. Patients were stratified by 1 vs. > 1 site of resected disease, and by disease-free interval ≤ vs. > 1 year. Clinical assessment for toxicity and patient-reported outcomes were performed every 4 weeks, and restaging scans every 12 weeks. The study was designed to observe a 42% improvement in disease-free survival (DFS) from 25% to 45% at 3 years. Results: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events had been observed (92% information). The median follow-up from randomization was 30 months (range 0.4 – 66.5 months). The study did not meet the primary endpoint: hazard ratio (95% CI) for DFS was 0.85 (0.55, 1.31) p= 0.47 in favor of pazopanib. At the time of unblinding, 22/129 (17%) of subjects had died. The HR for overall survival (OS) was 2.65 (1.02, 6.9) in favor of placebo ( p= 0.05). Patient-reported outcomes and laboratory correlates will be reported separately. Conclusions: 52 weeks of pazopanib did not improve DFS compared to blinded placebo in patients with mRCC who were NED after metastasectomy. There was a trend toward worse overall survival with pazopanib. Clinical trial information: NCT01575548.

scholarly journals Prognostic Role of PD-L1 in Malignant Solid Tumors: A Meta-Analysis

2017 ◽  
Vol 32 (1) ◽  
pp. 68-74 ◽  
Author(s):  
Jung-Soo Pyo ◽  
Guhyun Kang ◽  
Jung Yeon Kim
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Renal Cell ◽  
Malignant Tumors ◽  
Meta Analysis ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Free Survival ◽  
Tumor Types ◽  
Disease Free

Purpose The aim of this study was to elucidate the rates and prognostic roles of programmed cell death ligand 1 (PD-L1) immunohistochemical (IHC) expression in various malignant tumors through a systematic review and meta-analysis. Method The current study included 16,176 patients from 97 eligible studies. We investigated PD-L1 expression and its correlation with survival rate in various malignant tumors. Results The estimated rate of PD-L1 IHC expression was 0.449 (95% confidence interval [CI] 0.404-0.495). The highest and lowest PD-L1 expression levels were found in thyroid cancer (0.829, 95% CI 0.781-0.868) and small-cell neuroendocrine carcinoma (0.005, 95% CI 0.000-0.080), respectively. PD-L1 expression was significantly correlated with poorer overall survival and disease-free survival rates (hazard ratios 1.276, 95% CI 1.097-1.486 and 1.304, 95% CI 1.034-1.644, respectively). However, PD-L1 IHC expression was significantly correlated with worse overall survival rates in patients with esophageal cancer and renal cell carcinoma and with worse disease-free survival rates in patients with colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. Conclusions Our results show that PD-L1 expression rates and the correlations with survival varied between tumor types. Detailed evaluation criteria for PD-L1 will have to be standardized before application to specific tumor types.

scholarly journals Predictive Ability for Disease-Free Survival of the GRade, Age, Nodes, and Tumor (GRANT) Score in Patients with Resected Renal Cell Carcinoma

2020 ◽  
Vol 14 (2) ◽  
pp. 98-104
Author(s):  
Alessio Cortellini ◽  
Sebastiano Buti ◽  
Melissa Bersanelli ◽  
Katia Cannita ◽  
Giada Pinterpe ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Multivariate Analysis ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Disease Free Survival ◽  
Free Survival ◽  
Risk Of Recurrence ◽  
Significant Difference ◽  
Disease Free

Background: Recently, the GRANT (GRade, Age, Nodes, and Tumor) score was validated through an adjuvant trial population. Methods: This retrospective study evaluated the performance of the GRANT score as a prognostic model for disease-free survival (DFS), compared to the University of California Los Angeles Integrated Staging System (UISS) score, in a “real-life” population of early renal cell carcinoma patients. A uni-/multivariate analysis of DFS was also performed, to weigh the roles of baseline clinical factors. Results: From February 1998 to January 2018, 134 consecutive patients were enrolled, of which 85 patients (63.4%) had a favorable GRANT score, 49 (36.6%) an unfavorable GRANT score, and 21 (15.7%), 84 (62.6%), and 29 (21.6%) patients had a low, intermediate, or high risk of recurrence according to the UISS score, respectively. The median follow-up was 96 months. The median DFS of the overall study population was 53.7 months (95% CI: 38.4-87.8). Only bilateral renal cell carcinoma (p = 0.0041), Fuhrman grade 3/4 (p = 0.0008), pT3b- 4 (p = 0.0324), and pN1-2 (p = 0.0303) pathological status were confirmed as independent predictors of a shorter DFS by the multivariate analysis. The median DFS of patients with favorable and unfavorable GRANT scores were 84.9 (95% CI: 49.8-129) and 38.4 months (95% CI: 24.4-87.8), respectively, with a statistically significant difference (p = 0.0147). The median DFS of patients with low, intermediate, and high risk of recurrence according to the UISS score were 92.3 (95% CI: 18.1-153.9), 51.7 (95% CI: 36.2-87.8), and 49.8 months (95% CI: 31.3-129), respectively, without statistically significant differences (p = 0.4728). DFS c-statistic values were 0.59 (95% CI: 0.51-0.67) and 0.51 (95% CI: 0.42-0.60) for the GRANT and the UISS scores, respectively. Conclusion: The GRANT score might be a useful tool that is user-friendly and easy to perform in clinical practice.

Sign in / Sign up

Export Citation Format

Share Document