Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma

Chamie, Karim; Donin, Nicholas M.; Klöpfer, Pia; Bevan, Paul; Fall, Barbara; Wilhelm, Olaf G.; Störkel, Stephan; Said, Jonathan; Gambla, Michael; Hawkins, Robert E.; Jankilevich, Gustavo; Kapoor, Anil; Kopyltsov, Evgeny; Staehler, Michael; Taari, Kimmo; Wainstein, Alberto Julius Alves; Pantuck, Allan J.; Belldegrun, Arie S.

doi:10.1001/jamaoncol.2016.4419

Cited by 115 publications

(86 citation statements)

References 29 publications

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“…Five-year DFS was similar to that observed in another contemporary trial. 8 Ongoing correlative analyses are designed to identify subsets that may benefit from adjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Treatment for High-Risk Clear Cell Renal Cancer

et al. 2017

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IMPORTANCE Given recently published results of a 750-patient adjuvant sunitinib trial showing improved disease-free survival (DFS), the appropriate strategy for treating high-risk patients is unclear. We sought to determine whether there is improved disease-free survival benefit to taking the active drug in patients with high-risk (pT3, pT4, node-positive) clear cell renal cancer (ccRCC) in the ASSURE trial (adjuvant sunitinib or sorafenib vs placebo in resected unfavorable renal cell carcinoma [RCC]), the largest adjuvant trial published to date. OBJECTIVE To evaluate DFS and overall survival (OS) in ccRCC high-risk patients randomized to sunitinib or sorafenib vs placebo among patients with stages comparable to other high-risk adjuvant trials. DESIGN, SETTING, AND PARTICIPANTS The DFS and OS at 10 years postactivation were calculated for 1069 patients in US and Canadian cooperative groups with high-risk patients who had ccRCC histology and pT3, pT4, or node-positive disease accrued between 2006 and 2010 to the double-blind randomized placebo-controlled phase 3 trial. Outcome analyses by dose quartiles of these patients receiving sunitinib or sorafenib were also performed. INTERVENTIONS Patients received 1 year of adjuvant sunitinib (50 mg), sorafenib (800 mg) daily, or equivalent placebo. The study was amended for patient intolerance to sunitinib (37.5 mg), sorafenib (400 mg) daily, or equivalent placebo with mandatory dose escalation if no serious adverse effects were experienced. MAIN OUTCOMES AND MEASURES Disease-free survival, defined as time from randomization to recurrence, second primary cancer, or death. RESULTS Of 1069 patients, 358 (243 [67.9%] men, 115 [32.1%] women) received sunitinib, 355 (248 [69.9%] men, 107 [30.1%] women) received sorafenib, and 356 (254 [71.3%] men, 102 [28.7%] women) received placebo as adjuvant therapy. The mean (SD) age for each group was 58.3 (10.6) years, 56.8 (10.3) years, and 57.5 (10.4) years, respectively. Five-year DFS rates were 47.7%, 49.9%, and 50.0%, respectively for sunitinib, sorafenib, and placebo (HR, 0.94 for sunitinib vs placebo; and HR, 0.90; 97.5%CI, 0.71–1.14 for sorafenib vs placebo), with 5-year OS of 75.2%, 80.2%, and 76.5%(HR, 1.06; 97.5%CI, 0.78–1.45; P = .66, sunitinib vs placebo; and HR, 0.80; 97.5%CI, 0.58–1.11; P = .12 for sorafenib vs placebo). There was no difference by dose quartile. CONCLUSIONS AND RELEVANCE Neither prognostic category of the tumor nor dose intensity of therapy altered the lack of difference in DFS or OS in this population of patients with high-risk ccRCC. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00326898

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“…Five-year DFS was similar to that observed in another contemporary trial. 8 Ongoing correlative analyses are designed to identify subsets that may benefit from adjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Treatment for High-Risk Clear Cell Renal Cancer

et al. 2017

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“…Finally, it is still unclear whether prolonging DFS has any real impact on OS. The results from the SORCE, ATLAS, and EVEREST trials will help us better define the role of targeted therapy in the adjuvant setting. The patients included in these trials are being treated with sorafenib, axitinib, or everolimus for 3 years, the ATLAS study includes only those who have tumors with clear‐cell histology subtype, whereas the EVEREST and SORCE studies include those who have tumors with any histology.…”

Section: The Role Of Systemic Therapy For Localized Diseasementioning

confidence: 99%

Treatment of renal cell carcinoma: Current status and future directions

Barata

Rini

2017

CA A Cancer J Clinicians

660

528

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Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents-including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor-have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society.

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“…Girentuximab was well tolerated, with toxicity rates comparable with placebo. Overall, however, there was no significant difference between girentuximab and placebo for DFS (HR 0.97, 95% CI 0.79–1.18) or OS (HR 0.99, 95% CI 0.74–1.32) …”

Section: Vaccines and Targeted Immunotherapymentioning

confidence: 99%

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives

et al. 2019

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Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high‐risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron‐sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double‐blind placebo‐controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma.

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Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma

Abstract: clinicaltrials.gov Identifier: NCT00087022.

Cited by 115 publications

References 29 publications

Adjuvant Treatment for High-Risk Clear Cell Renal Cancer

Adjuvant Treatment for High-Risk Clear Cell Renal Cancer

Treatment of renal cell carcinoma: Current status and future directions

Systemic therapy in the management of localized and locally advanced renal cell carcinoma: Current state and future perspectives

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