scholarly journals Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Rachna Raman ◽  
Daniel Vaena
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Immune Therapies ◽  
Localized Renal Cell Carcinoma ◽  
Metastatic Rcc

Localized renal cell carcinoma (RCC) is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR) inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer) has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

scholarly journals Treatment Options in Metastatic Renal Cell Carcinoma: Focus on mTOR Inhibitors

2010 ◽  
Vol 4 ◽  
pp. CMO.S1590 ◽  
Author(s):  
Sumanta Kumar Pal ◽  
Robert A. Figlin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Treatment Options ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Phase Iii

The agents currently approved for use in metastatic renal cell carcinoma (mRCC) can be divided broadly into two categories: (1) vascular endothelial growth factor receptor (VEGFR)-directed therapies or (2) inhibitors of the mammalian target of rapamycin (mTOR). The latter category includes everolimus and temsirolimus, both approved for distinct indications in mRCC. Everolimus gained its approval on the basis of phase III data showing a benefit in progression-free survival relative to placebo in patients previously treated with sunitinib and/or sorafenib. In contrast, temsirolimus was approved on the basis of a phase III trial in treatment-naïve patients with poor-risk mRCC, demonstrating an improvement in overall survival relative to interferon-alfa. While these pivotal trials have created unique positions for everolimus and temsirolimus in current clinical algorithms, the role of mTOR inhibitors in mRCC is being steadily revised and expanded through ongoing trials testing novel sequences and combinations. The clinical development of mTOR inhibitors is outlined herein.

scholarly journals The next 10 years: Challenges for the future and overcoming resistance to targeted therapies for renal cell carcinoma

2016 ◽  
Vol 10 (11-12) ◽  
pp. 256 ◽  
Author(s):  
Daniel Y.C. Heng
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Mtor Inhibitors ◽  
Systemic Treatments

The introduction of targeted therapies over the past 10 years revolutionized the treatment of metastatic renal cell carcinoma (mRCC). The next 10 years hold promise for even greater expansion of the therapeutic armamentarium for mRCC. A number of recently completed and ongoing trials have explored the use of antivascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors in the adjuvant setting, the use of predictive biomarkers to guide personalized medicine, as well as new systemic treatments and combination therapies for mRCC.

scholarly journals Evolving Treatment Paradigm in Metastatic Renal Cell Carcinoma

2017 ◽  
pp. 319-329
Author(s):  
David M. Gill ◽  
Neeraj Agarwal ◽  
Ulka Vaishampayan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Mtor Inhibitors ◽  
Treatment Paradigm

The treatment paradigm for advanced and metastatic renal cell carcinoma (mRCC) has evolved rapidly since the arrival of targeted therapies and novel immunotherapies. mRCC was previously treated only with cytokines. However, discoveries of mutations affecting the von Hippel–Lindau tumor suppressor gene (leading to increased expression of VEGF and hypoxia inducible factor/HIF-1) and of deregulations in the phosphatidylinositol-3 kinase/AKT/mTOR pathway (resulting in tumor angiogenesis, cell proliferation, and tumor growth) have led to the development of numerous targeted therapies. The U.S. Food and Drug Administration (FDA) has thus approved a total of nine targeted therapies since 2005, including VEGF tyrosine kinase inhibitors (sunitinib, pazopanib, axitinib, sorafenib, and lenvatinib), a monoclonal antibody targeting VEGF (bevacizumab), mTOR inhibitors (temsirolimus and everolimus), and a multityrosine kinase inhibitor (cabozantinib). Furthermore, the development of immune checkpoint inhibitors has again shifted the mRCC therapeutic landscape with the FDA’s approval of nivolumab. Herein, we discuss the unprecedented changes in the field of clear cell histology mRCC in both the first-line and salvage settings, and we also discuss future therapies and recommend a treatment paradigm on sequencing of these agents.

Paradigm towards Tailored Therapies and Complete Responses in the Treatment of Metastatic Renal Cell Carcinoma

2012 ◽  
Vol 08 (01) ◽  
pp. 30
Author(s):  
Mayer Fishman ◽  
Thomas Hutson ◽  
Neeraj Agarwal ◽  
Eric Jonasch ◽  
◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose

In recent years, the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of targeted therapies. Multitargeted kinase inhibitors (such as sunitinib, sorafenib, pazopanib, and axitinib), the vascular endothelial growth factor inhibitor bevacizumab, and mammalian target of rapamycin inhibitors (such as everolimus and temsirolimus) have become the standard of care for the palliation of metastatic disease. Unfortunately, cumulative toxicities and the lack of marked benefits have prevented the combined use of most molecularly targeted agents. Selected patients with mRCC benefit from immunotherapy, as subsets of patients can experience long-term disease remission or complete response with high-dose interleukin-2. In order to optimize the value of immunotherapy, improvements in the selection of drugs and combinations with novel immunomodulatory agents must be pursued.

Erlotinib with sirolimus for advanced renal cell carcinoma: Preliminary efficacy results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16037-e16037
Author(s):  
T. W. Flaig ◽  
L. Costa ◽  
K. Breaker ◽  
M. Schultz ◽  
F. Crighton ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Treated Patient ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Current Data ◽  
Pharmacokinetic Data ◽  
Data Set ◽  
Sorafenib Treatment

e16037 Background: The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Temsirolimus, an analog of rapamycin, prolongs survival when used to treat high-risk RCC patients and is approved for the treatment of advanced RCC. Oral rapamycin (sirolimus/Rapamune) is less expensive than temsirolimus and plasma levels can be routinely monitored. Pre-clinical data indicate that the combined inhibition of the epidermal growth factor receptor (EGFR) and mTOR results in enhanced anti-cancer activity, especially in cell lines with wt-VHL. Methods: All patients on this study had metastatic or unresectable renal cell carcinoma with progression despite sunitinib and/or sorafenib. Treatment was started with erlotinib (Tarceva) 150 mg po daily. On day 8, sirolimus was begun with a single 6 mg loading dose and then given as 2 mg daily. Radiographic assessments were performed every 8 weeks. Results: The current data set was obtained through July of 2008. Enrollment started in July of 2006 with the last patient accrued in March 2008; 25 patients have been treated. The median subject age was 60 years with an average of 2.6 previous medical treatments. The unconfirmed median progression free survival (PFS) was 12 weeks (range 2–52) with 4 patients remaining on active treatment and included in this analysis. No confirmed complete or partial responses were observed, but meaningful stable disease (SD) (e.g., > 6 months) was noted in a small group of patients. The most common adverse events were rash and diarrhea with the majority of these observed as a grade 1 event. Grade 3 and 4 toxicities included rash, mucositis, neurological motor weakness, dehydration, worsening cardiac function, non-ST elevation MI, and anemia. Additional efficacy, toxicity and pharmacokinetic data will be presented. Conclusions: The combination of erlotinib and sirolimus produces a median PFS of 12 weeks in a significantly pretreated RCC population, which is not dissimilar to recent results with other mTOR inhibitors in this setting. The toxicity profile of this combination is consistent with the expectations of this pre-treated patient population with advanced RCC. [Table: see text]

Activity of single-agent bevacizumab (B) in patients with metastatic renal cell carcinoma (RCC) previously treated with VEGF- and mTOR-based therapies.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 435-435
Author(s):  
Andrew J. Armstrong ◽  
James D. Turnbull ◽  
Julien Cobert ◽  
Tracy Jaffe ◽  
Michael Roger Harrison ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Mtor Inhibition ◽  
Grade 3

435 Background: Given a lack of clinical information on therapeutic efficacy of agents following progression after vascular endothelial growth factor (VEGF) tyrosine kinase inhibition (TKI) and mammalian target of rapamycin (mTOR) inhibition in metastatic renal cell carcinoma (mRCC), we investigated the activity of single agent bevacizumab (B) in this setting. Methods: We conducted a retrospective analysis of single agent B-treated patients with mRCC in the second/third line setting, and identified 21 subjects who met inclusion criteria. The primary endpoint was progression-free survival (PFS). Baseline characteristics, survival, response efficacy outcomes, and toxicities were assessed and summarized. Results: 21 patients (15 women/6 men) were treated with B at a dose of 5 mg/kg/week, dosed q2-3 weeks. Median age was 63, 80% were white, 14% black; 80% had clear cell histology. Median time from diagnosis to B therapy was 3 years (range 1-18); 100% had prior VEGF TKI therapy; 43% had prior mTOR inhibitor; 43% had prior IFN and 19% prior IL-2; median number of prior therapies was 3 (range 1-7); 100% were considered Motzer intermediate risk. Median PFS on B for all subjects was 4.4 mo (95% CI 2.8-9.6) and median OS was 19.4 mo (95% CI 9.9-NR) from start of B therapy. ORR was 2 CR/PR (9.5%), 11 SD (52%), 5 PD, 3 NE. For subjects treated with prior VEGF and mTOR inhibitors, median PFS and OS were 4.4/13.2 mo. Toxicities were as expected and severe adverse events included grade 3-4 fatigue (6), grade 3-4 dehydration (5), and grade 4 failure to thrive (2), grade 4 constipation (2), and grade 3 muscle weakness (2). Conclusions: Single agent B therapy has acceptable toxicity and moderate disease stabilizing activity in selected patients with mRCC who have failed prior VEGF TKI and mTOR inhibitor therapy, and suggests a benefit to continued ongoing VEGF inhibition. Further prospective study of B alone, in combination with mTOR inhibition, or with alternative targeted agents is warranted.

Mayo Adhesive Probability Score Is Associated With Localized Renal Cell Carcinoma Progression-free Survival

Urology ◽  
2016 ◽  
Vol 89 ◽  
pp. 54-62 ◽  
Author(s):  
David D. Thiel ◽  
Andrew J. Davidiuk ◽  
Camille Meschia ◽  
Daniel Serie ◽  
Kaitlynn Custer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival ◽  
Probability Score ◽  
Localized Renal Cell Carcinoma

scholarly journals Metastatic renal cell carcinoma: Current scenario and future trends

2012 ◽  
Vol 01 (01) ◽  
pp. 30-35
Author(s):  
Anubha Bharthuar
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Mtor Inhibitors ◽  
Phase Iii ◽  
The Novel ◽  
Optimal Dosing ◽  
Phase Iii Trials ◽  
Current Scenario ◽  
Metastatic Rcc

AbstractAn improved understanding of the biology of renal cell carcinoma (RCC) has led to the development of a number of targeted agents, which has resulted in a paradigm shift in the management of metastatic RCC. We review the current therapeutic strategies for metastatic RCC and present a synopsis of the novel agents in use today with a discussion of the phase III trials that demonstrated their clinical benefit. The management of RCC continues to evolve. The introduction of VEGF and mTOR inhibitors has markedly expanded our drug armamentarium and improved the outcome of a disease that has always been challenging to treat. Knowledge from upcoming trials will help us utilize these drugs for maximum clinical efficacy with optimal dosing and sequencing, either individually or in combination therapy.

Sign in / Sign up

Export Citation Format

Share Document