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

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

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.

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.

Sub-classification of patients with intermediate-risk metastatic renal cell carcinoma treated with targeted therapy

2019 ◽  
Vol 49 (8) ◽  
pp. 780-785
Author(s):  
Go Kaneko ◽  
Suguru Shirotake ◽  
Koshiro Nishimoto ◽  
Yasumasa Miyazaki ◽  
Keiichi Ito ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
High Risk ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Targeted Therapy ◽  
Laboratory Data ◽  
Original Model

Abstract Background International Metastatic Renal Cell Carcinoma Database Consortium model predicts the outcomes of metastatic renal cell carcinoma stratified into favorable, intermediate, and poor risk groups (FG, IG, and PG, respectively), with approximately 50% of patients being classified as IG. We aimed to generate better risk model based on the sub-classification of IG. Methods We analyzed records of 213 consecutive patients receiving molecular targeted therapy. Age, gender, histology, type of initial molecular targeted therapy, serum laboratory data, previous nephrectomy and immunotherapy, and metastatic sites were used for IG sub-stratification. Modified and original models were compared using a concordance correlation coefficient analysis. Results Median follow-up was 17.8 months. Serum albumin, serum C-reactive protein, and bone metastases were independent predictors of overall survival (OS) in IG. IG was sub-classified into low-, middle-, and high-risk IG according to the number of predictors. The following modified model was developed: modified FG (FG & low-risk IG), modified IG (middle-risk IG), and modified PG (PG & high-risk IG). Concordance indices for original and modified models were 0.68 and 0.73, respectively (P < 0.001). OS was significantly longer in modified PG treated with mammalian target of rapamycin inhibitors as second-line therapy than with tyrosine kinase inhibitors, whereas this was not observed in the original model. Conclusions We successfully developed modified IMDC model using a two-step process: the original IMDC plus an IG sub-stratification, and demonstrated that it predicts outcomes more accurately than original model.

Sign in / Sign up

Export Citation Format

Share Document