Armstrong, A.J., et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial.

Lancet Oncol, 2016. 17: 378

Conclusions: In patients with metastatic non-clear cell renal cell carcinoma, sunitinib improved progression-free survival compared with everolimus. Future trials of novel agents should account for heterogeneity in disease outcomes based on genetic, histological, and prognostic factors.

Lee, Z., et al. Local Recurrence Following Resection of Intermediate-High Risk Non-metastatic Renal Cell Carcinoma: An Anatomic Classification and Analysis of the ASSURE (ECOG-ACRIN E2805) Adjuvant Trial.

J Urol, 2020.203(4): 684

Conclusions: In patients with intermediate-high risk nonmetastatic renal cell carcinoma local recurrence appears to be a function of biology more than of surgical modality or surgery type. The prognosis for solitary intra-abdominal local recurrences appear similar regardless of location (types I-III). Local recurrences involving multiple sites and/or subdivisions are associated with worse survival (type IV).

Escudier  B.,  et  al.  Phase  III  trial  of  bevacizumab  plus  interferon  alfa-2a  in  patients  with  metastatic  renal  cell  carcinoma (AVOREN): final analysis of overall survival.

J ClinOncol, 2010. 28: 2144.

Conclusions: Bevacizumab plus IFN is active as first-line treatment in patients with mRCC. Most patients with mRCC receive multiple lines of therapy, so considering the overall sequence of therapy when selecting first-line therapy may optimize patient benefit.

Rini, B.I., et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.

Lancet, 2011. 378: 1931

Conclusions: Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma.

Choueiri, T.K., et al. CabozantinibVersusSunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.

J ClinOncol, 2017. 35: 591.

Conclusions: Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over standard-of-care sunitinib as first-line therapy in patients with intermediate- or poor-risk Mrcc

Rini,  B.I.,  et  al.  Bevacizumab  plus  interferon  alfa  compared  with  interferon  alfamonotherapy  in  patients  with  metastatic renal cell carcinoma:

CALGB 90206. J ClinOncol, 2008. 26: 5422.

Conclusions: Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.

Mejean A., et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma.

N Engl J Med, 2018. 379(5): 417

Conclusions: Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease.

Motzer, R.J., et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.

N Engl J Med, 2015. 373: 1803

Conclusions: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus.

Motzer,  R.J.,  et  al.  Nivolumab  plusIpilimumab  versus  Sunitinib  in  Advanced  Renal-Cell  Carcinoma. 

N  Engl  J  Med, 2018. 378: 1277.

Conclusions: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma.

Motzer, R.J., et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma.

N Engl J Med, 2013. 369: 722

Conclusions: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib.

Blom, J.H., et al. Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881.

EurUrol, 2009. 55: 28

Conclusions: This study shows that, after proper preoperative staging, the incidence of unsuspected lymph-node metastases is low (4.0%) and that, notwithstanding a possible relationship to this low incidence rate, no survival advantage of a complete lymph-node dissection in conjunction with a radical nephrectomy could be demonstrated.

Scosyrev, E., etal.Renal function after nephron-sparing surgery versus radical nephrectomy:

results from EORTC randomized trial 30904. EurUrol, 2014. 65: 372

Conclusions: Compared with RN, NSS substantially reduced the incidence of at least moderate renal dysfunction (eGFR<60), although with available follow-up the incidence of advanced kidney disease (eGFR<30) was relatively similar in the two treatment arms, and the incidence of kidney failure (eGFR<15) was nearly identical. The beneficial impact of NSS on eGFR did not result in improved survival in this study population.

Van Poppel, H., etal.A prospective randomized EORTC intergroup phase 3 study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma.

EurUrol, 2007. 51: 1606.

Conclusions: NSS for small, easily resectable, incidentally discovered RCC in the presence of a normal contralateral kidney can be performed safely with slightly higher complication rates than after RN. The oncologic results are eagerly awaited to confirm that NSS is an acceptable approach for small asymptomatic RCC

Van Poppel, H., et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma.

EurUrol, 2011. 59: 543.

Conclusions: Nephron sparing surgery and Radical Nephrectomy provide excellent oncologic results. In the Itention to treat population, NSS seems to be significantly less effective than RN in terms of OS. However, in the targeted population of RCC patients, the trend in favour of RN is no longer significant. The small number of progressions and deaths from renal cancer cannot explain any possible OS differences between treatment types.

Bissler, J.J., et al. Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study.

PLoSOne, 2017. 12: e0180939

Conclusions: Everolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use of everolimus as a viable treatment option for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.

Motzer,  R.J.,  et  al.  Avelumab  plusAxitinib  versus  Sunitinib  for  Advanced  Renal-Cell  Carcinoma. 

N  Engl  J  Med,  2019. 380: 1103.

Conclusions: Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma.

Rini, B.I., et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

N Engl J Med, 2019. 380: 1116.

Conclusions: Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib.

McDermott,  D.F.,  et  al.  Pembrolizumabmonotherapy  as  first-line  therapy  in  advanced  clear  cell  renal  cell  carcinoma (accRCC):

Results from cohort A of KEYNOTE-427. J ClinOncol, 2018. 36.

Conclusions: Pembromonotherapy demonstrated promising efficacy and acceptable tolerability in pts with accRCC. Potential tissue-based biomarkers associated with response will be presented.

Choueiri, T.K., etal.Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.

N Engl J Med, 2015. 373: 1814.

Conclusions: Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.

Rini,  B.I.,  et  al.  Tivozanib  versus  sorafenib  in  patients  with  advanced  renal  cell  carcinoma  (TIVO-3):  a  phase  3,  multicentre, randomised, controlled, open-label study.

Lancet Oncol, 2020. 21: 95

Conclusions: This study showed that tivozanib as third-line or fourth-line therapy improved progression-free survival and was better tolerated compared with sorafenib in patients with metastatic renal cell carcinoma

Motzer, R.J., et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.

N Engl J Med, 2007. 356: 115.

Conclusions: Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa

Hudes,  G.,  et  al.  Temsirolimus,  interferonalfa,  or  both  for  advanced  renal-cell  carcinoma. 

N  Engl  J  Med,  2007.  356: 2271

Conclusions: As compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis. The addition of temsirolimus to interferon did not improve survival.

Negrier,  S.,  et  al.  Medroxyprogesterone,  interferon  alfa-2a,  interleukin  2,  or  combination  of  both  cytokines  in  patients  with  metastatic  renal  carcinoma  of  intermediate  prognosis:  results  of  a  randomized  controlled  trial. 

Cancer, 2007. 110: 2468

Conclusions: Subcutaneous interleukin-2 and/or interferon-alfa provide no survival benefit in metastatic renal cancers of intermediate prognosis, and they induce a significant risk of toxicity. Newly available angiogenesis inhibitors should be preferred for these patients..

Escudier,  B.,  et  al.  Randomized,  controlled,  double-blind,  cross-over  trial  assessing  treatment  preference  for  pazopanib  versus  sunitinib  in  patients  with  metastatic  renal  cell  carcinoma: 

PISCES  Study.  J  ClinOncol,  2014.  32: 1412.

Conclusions: This innovative cross-over trial demonstrated a significant patient preference for pazopanib over sunitinib, with HRQoL and safety as key influencing factors.

Escudier,  B.,  et  al.  Open-label  phase  2  trial  of  first-line  everolimusmonotherapy  in  patients  with  papillary  metastatic renal cell carcinoma: RAPTOR final analysis.

Eur J Cancer, 2016. 69: 226

Conclusions: Results of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour.

Motzer,  R.J.,  et  al.  Efficacy  of  everolimus  in  advanced  renal  cell  carcinoma:  a  double-blind,  randomised,  placebo-controlled phase III trial.

Lancet, 2008.372: 449.

Conclusions: Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies.

Motzer, R.J., et al. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma.

J ClinOncol, 2014.32: 2765.

Conclusions: Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

Bex A, et al. Comparison of immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving Sunitinib: The SURTIME randomized clinical trial.

JAMA Oncol, 2019. 5(2): 164

Conclusions: Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib

Motzer, R.J., et al. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results.

EurUrol, 2018. 73: 62

Conclusions: A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy.