scholarly journals A prospective, open-label, interventional study protocol to evaluate treatment efficacy of nivolumab based on serum-soluble PD-L1 concentration for patients with metastatic and unresectable renal cell carcinoma

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e030522
Author(s):  
Yukari Bando ◽  
Nobuyuki Hinata ◽  
Takashi Omori ◽  
Masato Fujisawa
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Phase Iii ◽  
Power Calculation ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

IntroductionNivolumab has been proven to prolong overall survival as a second-line therapy for patients with advanced renal cell carcinoma (RCC) in a phase III clinical trial. However, versatile biomarkers have not been established to predict the efficacy of nivolumab against target disease.Methods and analysisAfter registration, screening test and serum-soluble programmed cell death 1-ligand 1 (sPD-L1) measurement will be performed by using the ELISA; patients will be grouped into high sPD-L1 or low sPD-L1 groups. Nivolumab (240 mg every 2 weeks by intravenous drip infusion) will be administered to each participant. For this prospective study, statistical power calculation indicated that 48 participants with metastatic or unresectable RCC are needed to assess the efficacy of this method. The participants must be at the age of at least 20 years at the time of informed consent and require second-line therapy after failure of first-line therapy or discontinuation due to adverse effects. All data will be collected in our institution. The primary endpoint is progression-free survival, and secondary endpoints are overall survival and objective response rate. In this protocol, we will examine sPD-L1 as a promising predictive marker.Ethics and disseminationThis protocol was approved by the Kobe University Clinical Research Ethical Committee (C180067). Findings of this study will be widely disseminated through conference presentations, reports, factsheets and academic publications; further generalisation will also be discussed.Trial registration numberUMIN000027873.

Sunitinib, sorafenib, temsirolimus, or bevacizumab in the treatment of metastatic renal cell carcinoma (RCC): A review of health economic evaluations

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17539-e17539
Author(s):  
J. Norum ◽  
C. Nieder ◽  
M. Kondo
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cost Effectiveness ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Economic Evaluations ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Wide Range

e17539 Background: Renal cell carcinoma (RCC) is the most prevalent kidney cancer and the 5-year overall survival figure in metastatic disease (mRCC) is about 10%. New targeted drugs (sunitinib, sorafenib, bevacizumab, temsirolimus) have shown activity in the treatment of mRCC, but they are all associated with a significant burden of cost. Methods: To support decision makers in their allocation of resources, cost-effectiveness models are constructed to compare the costs and outcomes of anticancer therapy. The PubMed, ASCO abstracts, Google, and the Igaku Chuo Zasshi databases were searched in November 2008 with key terms: kidney, renal, cancer, cost, sunitinib, sorafenib, temsirolimus, and bevacizumab. Seven studies reporting data on cost-effectiveness were revealed. Three of them were published in full text versions. The countries of application were United Kingdom, Canada, United States, Finland, and Japan. An analytical checklist was applied to the seven economic evaluations. Results: The review reveals figures of cost per LYG or QALY in the range €22,648 to €203,692, depending on line setting and drug focused. The results were limited by short follow up periods and the consequently fact that premature data had to be implemented in the Markov models. When compared, sunitinib has the lowest cost-effectiveness figure. Second-line therapy dose not seem to offer valid incremental cost-effectiveness ratios (ICERs) below accepted cost-effectiveness thresholds. As long as cross-over to the experimental arm is allowed (based on improvement in progression free survival) overall survival data are difficult to interpret and the cost difference between the treatment and the control arm minimised. Conclusions: The review revealed ICERs with a wide range. Sunitinib has the lowest cost-effectiveness figure. Second-line therapy does not look cost-effective. [Table: see text]

scholarly journals Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma

2014 ◽  
Vol 32 (8) ◽  
pp. 760-767 ◽  
Author(s):  
Thomas E. Hutson ◽  
Bernard Escudier ◽  
Emilio Esteban ◽  
Georg A. Bjarnason ◽  
Ho Yeong Lim ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Therapy ◽  
Phase Iii Trial ◽  
Line Therapy

Purpose This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib. Patients and Methods In total, 512 patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (≤ or > 180 days), prognostic risk, histology (clear cell or non–clear cell), and nephrectomy status. The primary end point was progression-free survival (PFS) by independent review committee assessment. Safety, objective response rate (ORR), and overall survival (OS) were secondary end points. Results Primary analysis revealed no significant difference between treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% CI, 0.71 to 1.07; two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively. There was a significant OS difference in favor of sorafenib (stratified HR, 1.31; 95% CI, 1.05 to 1.63; two-sided P = .01). Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months, respectively. Safety profiles of both agents were consistent with previous studies. Conclusion In patients with mRCC and progression on sunitinib, second-line temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC.

Second-line therapy for refractory renal-cell carcinoma

2012 ◽  
Vol 83 (1) ◽  
pp. 112-122 ◽  
Author(s):  
Fable Zustovich ◽  
Giuseppe Lombardi ◽  
Ornella Nicoletto ◽  
Davide Pastorelli
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Third-line therapy in metastatic renal cell carcinoma: Results from the International mRCC Database Consortium.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 430-430 ◽  
Author(s):  
Daniel Yick Chin Heng ◽  
Connor Wells ◽  
Frede Donskov ◽  
Brian I. Rini ◽  
Jae-Lyun Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Second Line ◽  
Second Line Therapy ◽  
Therapy Initiation ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

430 Background: Third-line targeted therapy efficacy in metastatic renal cell carcinoma (mRCC) is not well characterized and many funding bodies do not provide reimbursement for it. Methods: The International mRCC Database Consortium (IMDC) consists of consecutive patient series from 25 cancer centers. It was queried for specific sequences of targeted therapy and third-line therapy. Kaplan Meier estimates were used for survival. Cox proportional hazards models were used to adjust hazard ratios for confounders. Patients that stopped second-line therapy were divided into two groups: those that went onto third-line therapy and those did not. Results: 4,050 patients were treated with first-line targeted therapy, of which 2,011 (49.6%) had second-line therapy and 879 (21.7%) had third-line targeted therapy. The most common third-line therapies were everolimus 25%, sorafenib 14%, sunitinib 13%, temsirolimus 11%, pazopanib 10%, and axitinib 6%. IMDC prognostic groups at third-line therapy initiation were 6% favorable risk, 67% intermediate risk, and 27% poor risk. Overall response rate for third-line therapy was 10.5% and 50.9% had stable disease in those patients that were evaluable. Median PFS was 5.1 months (95% CI, 4.5-5.7) and median OS from third-line therapy initiation was 12.0 months (95% CI, 10.7-12.9). Patients stopping second-line therapy that move on to third-line therapy vs. those that do not receive third line therapy have a median OS from stopping second-line therapy of 13.1 vs. 2.3 mons (p<0.0001). When adjusted for second-line IMDC prognostic criteria and KPS at second-line treatment cessation, patients who do receive third-line therapy have a HR of death of 0.41 (95% CI, 0.32-0.52; p<0.0001) compared to those that do not receive third-line therapy. This may be in part due to patient selection. To further limit bias, when excluding patients that live less than 3 months after second-line therapy cessation, the adjusted HR was similar. Conclusions: Third-line targeted therapy has demonstrated activity and is prevalent in use. Further studies are required to determine appropriate sequencing.

scholarly journals The Role of Everolimus in Renal Cell Carcinoma

2015 ◽  
Vol 2 (4) ◽  
pp. 187-194
Author(s):  
Malek Meskawi ◽  
Roger Valdivieso ◽  
Paolo Dell’Oglio ◽  
Vincent Trudeau ◽  
Alessandro Larcher ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Phase Iii ◽  
Current Evidence ◽  
Second Line ◽  
Cell Renal Cell Carcinoma ◽  
Line Therapy

Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

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