Phase 3, randomized, double-blind trial of pembrolizumab in the adjuvant treatment of renal cell carcinoma (RCC): KEYNOTE-564.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS712-TPS712 ◽  
Author(s):  
David I. Quinn ◽  
Tian Zhang ◽  
Howard Gurney ◽  
Gurjyot K. Doshi ◽  
Patrick Wayne Cobb ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Disease Recurrence ◽  
Adjuvant Setting ◽  
Phase 3 ◽  
Double Blind ◽  
Ecog Ps ◽  
Disease Free

TPS712 Background: Most patients with intermediate- to high-risk advanced renal cell carcinoma (RCC) will progress within 3 years following nephrectomy. Novel treatments in the adjuvant setting are needed to prevent disease recurrence in these higher-risk patients. Upregulation of the programmed death 1 (PD-1) pathway is associated with more aggressive disease and poor prognosis. PD-1 inhibitors have demonstrated activity in metastatic RCC, and PD-1 may represent a novel therapeutic target in the adjuvant setting. Pembrolizumab, a PD-1 inhibitor, blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Methods: KEYNOTE-564 (NCT03142334) is a randomized, double-blind, placebo-controlled phase 3 trial designed to evaluate the efficacy and safety of pembrolizumab as adjuvant therapy in patients with RCC. Eligibility criteria include age ≥18 years; intermediate- to high-risk (T2 grade 4, T3), high-risk (T4, T), or M1 NED RCC with a clear cell component; no prior systemic therapy for advanced RCC; disease free following complete or partial nephrectomy (and metastasectomy in patients with M1 NED) with negative surgical margins; Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1; and provision of a tumor sample for biomarker analyses. Patients will be randomly assigned (1:1) to pembrolizumab 200 mg administered intravenously every 3 weeks or placebo. Randomization will be stratified by metastasis stage (M0 vs M1 NED); within the M0 group, randomization will be further stratified by ECOG PS (0 vs 1) and region (US vs rest of world). Treatment will continue until disease recurrence, unacceptable toxicity, or the completion of 17 cycles (~1 year). Imaging will be performed every 12 weeks. The primary end point is disease-free survival (DFS) per investigator assessment. The key secondary end point is overall survival (OS). Other secondary objectives include safety, disease recurrence-specific survival, DFS and OS according to PD-L1 expression status, and patient-reported outcomes. Biomarkers that may be associated with response will be evaluated as an exploratory objective. Enrollment is ongoing and will continue until ~950 patients are enrolled. Clinical trial information: NCT03142334.

ATLAS study: A randomized double-blind phase 3 study of adjuvant axitinib versus placebo in subjects at high risk of recurrent renal cell carcinoma (RCC).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS4595-TPS4595 ◽  
Author(s):  
Tae Gyun Kwon ◽  
Seo Seong ◽  
Seok-Soo Byun ◽  
Hideaki Miyake ◽  
Takeshi Ueda ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Phase 3 ◽  
Double Blind ◽  
Recurrent Renal Cell Carcinoma

scholarly journals Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial

The Lancet ◽  
2016 ◽  
Vol 387 (10032) ◽  
pp. 2008-2016 ◽  
Author(s):  
Naomi B Haas ◽  
Judith Manola ◽  
Robert G Uzzo ◽  
Keith T Flaherty ◽  
Christopher G Wood ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

Understanding the adverse event experience in the S-TRAC adjuvant trial of sunitinib for high-risk renal cell carcinoma

2020 ◽  
Vol 16 (4) ◽  
pp. 39-47
Author(s):  
Sarah Yenser Wood ◽  
Joanne C Ryan ◽  
Andrew G Clair ◽  
Daniel J George
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Event ◽  
High Risk ◽  
Cell Carcinoma ◽  
Adjuvant Treatment ◽  
Renal Cell ◽  
Disease Recurrence ◽  
Event Management ◽  
The Usa ◽  
Metastatic Rcc

Until recently, the sole treatment for patients with nonmetastatic renal cell carcinoma (RCC) was nephrectomy followed by observation. As metastatic RCC (mRCC) remains largely incurable (5-year survival rate ∼12%), adjuvant treatment, with potential to prevent/delay disease recurrence, is needed. In November 2017, sunitinib was approved in the USA as the first adjuvant therapy for patients at high risk for recurrent RCC postnephrectomy based on results from the S-TRAC trial. Patients eligible for adjuvant treatment have no evidence of disease and may be less willing to tolerate side effects. Therefore, proactive adverse event management is critical for keeping patients on adjuvant treatment and requires understanding the subtle differences in the adverse event profile of sunitinib in the adjuvant versus metastatic RCC setting.

scholarly journals The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort

BMC Medicine ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Tobias Klatte ◽  
Kevin M. Gallagher ◽  
Luca Afferi ◽  
Alessandro Volpe ◽  
Nils Kroeger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Model ◽  
Disease Recurrence ◽  
Intermediate Risk ◽  
Net Benefit ◽  
Prognostic Groups ◽  
Risk Patients

Abstract Background The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery. Methods We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1–4, N0–1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups. Results We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups. Conclusions We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.

scholarly journals Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse: Results From the SORCE Randomized Phase III Intergroup Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4064-4075
Author(s):  
Tim Eisen ◽  
Eleni Frangou ◽  
Bhavna Oza ◽  
Alastair W.S. Ritchie ◽  
Benjamin Smith ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Outcome Analysis ◽  
Double Blind ◽  
Risk Of Recurrence

PURPOSE SORCE is an international, randomized, double-blind, three-arm trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) found to be at intermediate or high risk of recurrence. PATIENTS AND METHODS We randomly assigned participants (2:3:3) to 3 years of placebo (arm A), 1 year of sorafenib followed by 2 years of placebo (arm B), or 3 years of sorafenib (arm C). The initial sorafenib dose was 400 mg twice per day orally, amended to 400 mg daily. The primary outcome analysis, which was revised as a result of external results, was investigator-reported disease-free survival (DFS) comparing 3 years of sorafenib versus placebo. RESULTS Between July 2007 and April 2013, we randomly assigned 1,711 participants (430, 642, and 639 participants in arms A, B, and C, respectively). Median age was 58 years, 71% of patients were men, 84% had clear cell histology, 53% were at intermediate risk of recurrence, and 47% were at high risk of recurrence. We observed no differences in DFS or overall survival in all randomly assigned patients, patients with high risk of recurrence, or patients with clear cell RCC only. Median DFS was not reached for 3 years of sorafenib or for placebo (hazard ratio, 1.01; 95% CI, 0.83 to 1.23; P = .95). We observed nonproportional hazards; the restricted mean survival time (RMST) was 6.81 years for 3 years of sorafenib and 6.82 years for placebo (RMST difference, 0.01 year; 95% CI, −0.49 to 0.48 year; P = .99). Despite offering treatment adaptations, more than half of participants stopped treatment by 12 months. Grade 3 hand-foot skin reaction was reported in 24% of participants on sorafenib. CONCLUSION Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence after nephrectomy and is the appropriate control of our current international adjuvant RCC trial, RAMPART.

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.

Effect of salvage radiofrequency ablation on local control of recurrent renal cell carcinoma.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 355-355
Author(s):  
S. P. Psutka ◽  
A. Daha ◽  
D. Gervais ◽  
A. S. Feldman
Keyword(s):  
Renal Cell Carcinoma ◽  
Radiofrequency Ablation ◽  
Cell Carcinoma ◽  
Local Control ◽  
Renal Cell ◽  
Recurrent Disease ◽  
Complete Response ◽  
Disease Recurrence ◽  
Disease Free

355 Background: Radiofrequency ablation (RFA) has emerged as a safe and efficacious option to manage small renal cell carcinoma (RCC) in patients for whom comorbidities preclude surgical treatment. Salvage surgical excision of disease recurrence after ablative therapy is often complicated by extensive perinephric fibrosis. There are no reports in the literature which assess salvage RFA (sRFA) of recurrent disease (RD). The aim of this study was to assess the overall efficacy, complications, and safety of sRFA. Methods: Between 1998 and 2008, 313 patients underwent RFA for RCC. RD was defined as detectable new enhancing tissue in the prior RFA-cavitation site after a documented complete response. We retrospectively compared patients who developed RD (RD+, n = 15, 5.1%) with patients who remained disease free after a complete response (RD−, n = 296, 95%), assessing tumor characteristics (size, location, biopsy pathology), complications, and disease-free survival. Mean follow-up was 3 years (SD 2.1). Results: RD+ and RD− groups did not differ significantly in age, gender, or tumor type. In tumors < 4cm, 3.3% were RD+. In tumors >= 4cm, 9.6% were RD+ (p<0.0001). RD+ groups were more likely to have central tumors (20% vs. 5.7%, p = 0.04). Mean time to disease recurrence was 1.47 years (SD 0.75, 0.5-3.5 yrs). Of the 15 patients with RD, 7 patients underwent sRFA, 6 patients elected observation due to comorbidities precluding further treatment, one patient received chemotherapy for widespread metastases and one patient underwent salvage partial nephrectomy, which was aborted due to extensive tumor burden and perirenal fibrosis. There were no complications related to sRFA. Of those who underwent sRFA, local recurrences were successfully ablated in 100% of cases with a single salvage RFA treatment. None of these sRFA cases developed locally recurrent disease at an average of 3 years follow-up. Conclusions: RD after RFA remains challenging to treat due to the significant comorbidities of the patients who are candidates for ablative treatment of RCC. RD was more likely to occur in centrally located tumors, > 4cm in size. Salvage RFA successfully can achieve local control in these patients without increased rates of complications. No significant financial relationships to disclose.

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