Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immune Checkpoint Inhibitors in the Treatment of Renal Cell Carcinoma.

ABSTRACT: Immune checkpoint inhibitors have quickly become a critical component to the management of advanced renal cell carcinoma. These therapies have been approved for patients who are treatment-naive and who have progressed on antiangiogenesis agents. Combinations of immune checkpoint inhibitors with antiangiogenesis agents show significant response rates and prolong survival. Adverse events associated with the use of checkpoint inhibition present unique challenges in the management of patients, and careful considerations are needed when checkpoint inhibitors are combined with antiangiogenesis agents. Nevertheless, the improvement in overall survival associated with these agents indicates that they will remain a vital component of kidney cancer treatment.

SUBMITTER: Parikh M

PROVIDER: S-EPMC7164329 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Immune Checkpoint Inhibitors in the Treatment of Renal Cell Carcinoma.

Parikh Mamta M Bajwa Poornima P

Seminars in nephrology 20200101 1

Immune checkpoint inhibitors have quickly become a critical component to the management of advanced renal cell carcinoma. These therapies have been approved for patients who are treatment-naive and who have progressed on antiangiogenesis agents. Combinations of immune checkpoint inhibitors with antiangiogenesis agents show significant response rates and prolong survival. Adverse events associated with the use of checkpoint inhibition present unique challenges in the management of patients, and c ...[more]

PMID: 32130969

Similar Datasets

Immune checkpoint inhibitors in renal cell carcinoma.

Project description:The immune system has long been known to play a critical role in the body's defence against cancer, and there have been multiple attempts to harness it for therapeutic gain. Renal cancer was, historically, one of a small number of tumour types where immune manipulation had been shown to be effective. The current generation of immune checkpoint inhibitors are rapidly entering into routine clinical practice in the management of a number of tumour types, including renal cancer, where one drug, nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody (mAb), is licensed for patients who have progressed on prior systemic treatment. Ongoing trials aim to maximize the benefits that can be gained from this new class of drug by exploring optimal timing in the natural course of the disease as well as combinations with other checkpoint inhibitors and drugs from different classes.

| S-EPMC5869245 | biostudies-literature

Outcome of immune checkpoint inhibitors in metastatic renal cell carcinoma across different treatment lines.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC). Prospective trials have focused on ICI treatment in the first or second line. The aim of this analysis is to evaluate the benefit of ICI across different treatment lines.Patients and methodsThis is a single-center retrospective study that included mRCC patients who received ICIs in various treatment lines. Objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated.ResultsNinety-four patients were eligible for full evaluation. Patients were classified as International mRCC Database Consortium (IMDC) risk group categorization as good, intermediate and poor risk in 26.8%, 61.6% and 14.8% of cases, respectively. They were treated with ICI monotherapy, dual ICI therapy and ICI + tyrosine kinase inhibitor in 59%, 20% and 21% of cases, respectively. ORR, median PFS and OS for the entire cohort was 39.4%, 9.67 months [95% confidence interval (CI) 6.9-12.4 months] and 23.6 months (95% CI 13.3-33.9 months), respectively. The ORR by treatment line was 33% in first, 40.4% in the second, 35% in the third and 43.5% in the fourth line and beyond. Median PFS by treatment line was 8.6, 10.3, 7.9 and 7.23 months, respectively. The median OS was not reached in first-line treatment and was 26.2, 18.1 and 20.7 months in the second, third and fourth line and beyond, respectively.ConclusionsICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.

| S-EPMC8261552 | biostudies-literature

Immune checkpoint inhibitors in non-conventional histologies of renal-cell carcinoma.

Project description:For years, prospective randomized clinical trials excluded patients with non-conventional histologies of renal cell carcinoma (RCC). The paucity of data has led to adopting the same treatment strategies used for clear-cell RCC (ccRCC). In the present narrative review, we explored state of the art about use of immune checkpoint inhibitors (ICIs) in variant histologies of RCC. According to the results collected, ICIs as monotherapy showed promising antitumor activity in advanced non-clear cell (ncc)RCC. The objective response rate (ORR) was similar to that observed with single-agent anti-PD-1 in the ccRCC population, either in the first-line or the second-line setting, and responder patients experienced an early and durable benefit. Combined ICI-based strategies have shown increasing evidence in nccRCC and robust results in the sarcomatoid variants of RCC. A definitive recommendation about treating non-conventional histologies, either in adjuvant or metastatic settings, should be supported by more extensive dedicated trials.

| S-EPMC10012923 | biostudies-literature

A Contemporary Review of Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma.

Project description:The use of checkpoint inhibitors in advanced and metastatic renal cell carcinomas (RCCs) has rapidly evolved over the past several years. While immune-oncology (IO) drug therapy has been successful at resulting in improved responses and survival, combination therapies with immune checkpoint inhibitors and vascular endothelial growth factor (VEGF) inhibitors have further improved outcomes. This article reviews the landmark trials that have led to the approval of IO therapies, including the Checkmate 214 trial and combination IO/VEGF TKI therapies with Checkmate 9ER, CLEAR, and Keynote-426, and it includes a discussion on promising therapies moving in the future.

| S-EPMC8402652 | biostudies-literature

Immune checkpoint blockade in renal cell carcinoma.

Project description:Immune checkpoint blockade (ICB) is the foundation of current first-line therapies in patients with metastatic renal cell carcinoma (mRCC) with the potential for eliciting long-lasting remissions. With the expanding arsenal of ICB-based therapies, biomarkers of response are urgently needed to guide optimal therapeutic selection. We review the data behind ICB therapy in RCC, emerging biomarkers of response, and the evolving role of surgery in patients with mRCC.

| S-EPMC8364550 | biostudies-literature

Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors.

Project description:While head and neck squamous cell carcinomas (HNSCC) are marginally decreasing due to the reduction in exposure to the major risk factors, tobacco and alcohol, the incidence of high-risk human papillomavirus (HPV)-positive oropharynx squamous cell carcinomas (OPSCC), especially those in the tonsil and base of tongue subsites, are increasing. Patients with the latter are younger, display a longer overall survival, and show a lower recurrence rate after standard-of-care treatment than those with HPV-negative OPSCC. This may reflect an important role for immune surveillance and control during the natural history of the virally driven tumour development. Immune deviation through acquisition of immune-suppressive factors in the tumour microenvironment (TME) is discussed in relation to treatment response. Understanding how the different immune factors are integrated in the TME battleground offers opportunities for identifying prognostic biomarkers as well as novel therapeutic strategies. OPSCC generally receive surgery or radiotherapy for early-stage tumour treatment, but many patients present with locoregionally advanced disease requiring multimodality therapies which can involve considerable complications. This review focuses on the utilization of newly emerged immune checkpoint inhibitors (PD-1/PD-L1 pathway) for treatment of HNSCC, in particular HPV-positive OPSCC, since they could be less toxic and more efficacious. PD-1/PD-L1 expression in the TME has been extensively investigated as a biomarker of patient response but is yet to provide a really effective means for stratification of treatment. Extensive testing of combinations of therapeutic approaches by types and sequencing will fuel the next evolution of treatment for OPSCC.

| S-EPMC8310271 | biostudies-literature

Fat Loss in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

Project description:The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < -5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07-2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17-2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.

| S-EPMC9967473 | biostudies-literature

Treatment-free survival after discontinuation of immune checkpoint inhibitors in metastatic renal cell carcinoma: a systematic review and meta-analysis.

Project description:While immune checkpoint inhibitors (ICI) can lead to sustained responses in metastatic renal cell carcinoma (mRCC), the optimal duration of therapy remains unknown. We aimed to examine treatment-free survival (TFS) in objective responders who discontinued ICI and to explore factors that may impact objective response rate (ORR) and TFS. MEDLINE/PubMed, Embase, and the Cochrane Library were searched for prospective studies reporting individual outcomes after ICI discontinuation in patients with mRCC. Pooled ORR and TFS were estimated using random-effects meta-analyses, and associations between ICI regimen type or treatment line and ORR or TFS were evaluated. Sixteen cohorts comprising 1833 patients treated with ICI were included. The pooled ORR was 43% (95% CI 33% to 53%), and significant differences in summary estimates existed among patients who received ICI monotherapy (22%, 95% CI 18% to 26%), ICI plus a vascular endothelial growth factor (VEGF) pathway inhibitor (57%, 95% CI 48% to 65%), and dual ICI (40%, 95% CI 36% to 44%). Of 572 responders who had available data, 327 stopped ICI, with 86 (26%) continuing to respond off-treatment. Pooled TFS rates at 6 and 12 months were 35% (95% CI 20% to 50%) and 20% (95% CI 8% to 35%), respectively, and were highest for responders treated with dual ICI and lowest for those treated with ICI plus a VEGF pathway inhibitor. Thus, a subset of patients with mRCC who are treated with ICI-based therapy can have durable TFS after therapy discontinuation. Prospective clinical trials and biomarkers are needed to identify patients who can discontinue ICI therapy without compromising clinical outcomes.

| S-EPMC8488739 | biostudies-literature

Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma.

Project description:Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies.

| S-EPMC8183071 | biostudies-literature

Combinations of Anti-Angiogenic Agents and Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Best Option?

Project description:Over the past decade, major advances have been made in the treatment of advanced and metastatic renal cell carcinomas, specifically clear cell carcinomas. For many years the optimal approach was sequential; thus, monotherapies [principally tyrosine kinase inhibitors (TKIs)] targeting angiogenesis until toxicity or progressive disease developed. The rationale was the common mechanisms of action of the targeting agents and avoidance of the risk of overlapping toxicities. Immune checkpoint inhibitors (ICIs) are effective monotherapies, and combinations thereof with anti-angiogenic agents were thus later considered. Synergistic interactions were reported in vitro. Clinical efficacy was evident in three pivotal phase III trials with axitinib-pembrolizumab, cabozantinib-nivolumab, and lenvatinib-pembrolizumab combinations. Two other combinations showed interesting results but did not improve overall survival. However, the data aided our understanding of the new therapeutic approaches. A combination of the ICIs nivolumab and ipilimumab was the first to evidence better progression-free and overall survival compared to sunitinib in patients with intermediate or unfavourable prognoses as evaluated by the International mRCC Database Consortium (IMDC). Here we focus on the TKI-ICI combinations, emphasising the rationale of their use and the clinical results. To date, no biomarker facilitating the selection of an optimal treatment by disease and patient status has been reported.

| S-EPMC9954176 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data