Adjuvant therapy for advanced renal cell carcinoma

Meissner, Matthew; McCormick, Barrett Z.; Karam, Jose A.; Wood, Christopher G.

doi:10.1080/14737140.2018.1469980

Cited by 17 publications

(13 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To improve these results, the role of adjuvant treatments after surgery is being investigated to eliminate possible foci of clinically undetectable micrometastases [7]. Several adjuvant strategies, including cytokine therapy, radiotherapy, and hormone therapy, have been explored to decrease the rate of relapse, but none have been successful.…”

Section: Introductionmentioning

confidence: 99%

“…Several adjuvant strategies, including cytokine therapy, radiotherapy, and hormone therapy, have been explored to decrease the rate of relapse, but none have been successful. The proven efficacy of antiangiogenic therapies, including the vascular endothelial growth factor (VEGF) pathway inhibitors in patients with metastatic renalcell carcinoma (mRCC) supports the evaluation of these drugs as adjuvant therapy [7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adjuvant Treatment for High-Risk Clear Cell Renal Cancer

et al. 2017

View full text Add to dashboard Cite

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

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adjuvant Treatment for High-Risk Clear Cell Renal Cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Of note, all studies considered in our analysis adopted different selection modalities with a not negligible heterogeneity in terms of tumour stages, risk of recurrence and tumour subtypes included. In fact, the S-TRAC trial enrolled a higher-risk population and the study protocol had important restrictions on histologic subtypes compared with ASSURE, something that could have played an important role in the highest DFS benefit observed in S-TRAC (9,10). More specifically, one-third of patients of the ASSURE trial had low-risk tumours-pT1 and pT2-and the ATLAS and the PROTECT studies included an important proportion of these patients (11% and 14%, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, adjuvant treatment in RCC is still a problematic issue despite several adjuvant therapies have been tested in an attempt to improve clinical outcomes for RCC patients (9). Indeed, none of the compounds evaluated in this field have shown a convincing clinical benefit justifying an inclusion in clinical practice (10).…”

Section: Review Article On Update On Molecular Classification and Indmentioning

confidence: 99%

Adjuvant therapy in renal cell carcinoma: is it the right strategy to inhibit VEGF?

et al. 2021

View full text Add to dashboard Cite

Despite several clinical trials have assessed different agents in the adjuvant setting, renal cell carcinoma (RCC) still remains a disease orphan of an effective adjuvant treatment. In fact, systemic therapies targeting angiogenesis that have been observed to be effective in metastatic setting failed to show an improvement in terms of clinical outcomes when used ad adjuvant treatments. In this study, we performed a meta-analysis of 5 randomized clinical trials to assess the impact of tyrosine kinase inhibitors (TKIs) targeting angiogenesis after surgery: ASSURE, S-TRAC, PROTECT, ATLAS, SORCE. Among the 6,531 patients assessed, we confirmed the lack of efficacy of adjuvant treatments in terms of diseasefree survival (DFS) (pooled-HR 0.93, 95% CI, 0.84-1.02, P=0.16) and overall survival (OS) (pooled-HR 0.98, 95% CI, 0.88-1.09, P=0.54). To the best of our knowledge, we still ignore why some treatments active in the metastatic setting do not show similar efficacy as adjuvant treatment. Exploring possible reasons of this apparently conflicting results is important as it may offer new insights that should be evaluated in next generation adjuvant trials. Immune checkpoint inhibitors (ICIs) have reported significant results-as monotherapy or in combinations with other anticancer agents-in metastatic setting, and the results of trials evaluating these agents in the adjuvant setting are awaited.

show abstract

“…Clinical trials looking at the overall survival benefit and toxicity of sunitinib, pazopanib, and axitinib have shown no improvement in overall survival and an increase in toxicity. 27 Only one study with sunitinib conducted during the modern age of RCC care has shown an increase in progression-free survival (PFS), but also showed a much higher frequency of grade 3 and grade 4 adverse events. 28…”

Section: Treatment Of Localized Diseasementioning

confidence: 99%