scholarly journals Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma

2019 ◽  
Vol 20 (7) ◽  
pp. 1692 ◽  
Author(s):  
Solène-Florence Kammerer-Jacquet ◽  
Antoine Deleuze ◽  
Judikaël Saout ◽  
Romain Mathieu ◽  
Brigitte Laguerre ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Pathologic Features ◽  
Death Receptor Ligand ◽  
Antiangiogenic Drugs

Renal cell carcinoma encompass distinct diseases with different pathologic features and distinct molecular pathways. Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1) / programmed death receptor 1 (PD-1) pathway alone or in combination have greatly changed clinical management of metastatic renal cell carcinoma, now competing with antiangiogenic drugs in monotherapy for first-line treatment. However, long-term response rates are low, and biomarkers are needed to predict treatment response. Quantification of PD-L1 expression by immunohistochemistry was developed as a promising biomarker in clinical trials, but with many limitations (different antibodies, tumour heterogeneity, specimens, and different thresholds of positivity). Other biomarkers, including tumour mutational burden and molecular signatures, are also developed and discussed in this review.

scholarly journals Renal Cell Carcinoma in the Era of Precision Medicine: From Molecular Pathology to Tissue-Based Biomarkers

2018 ◽  
Vol 36 (36) ◽  
pp. 3553-3559 ◽  
Author(s):  
Sabina Signoretti ◽  
Abdallah Flaifel ◽  
Ying-Bei Chen ◽  
Victor E. Reuter
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Molecular Features ◽  
Pathologic Features ◽  
Clear Cell Rcc ◽  
Metastatic Rcc

Renal cell carcinoma (RCC) is not a single entity but includes various tumor subtypes that have been identified on the basis of either characteristic pathologic features or distinctive molecular changes. Clear cell RCC is the most common type of RCC and is characterized by dysregulation of the von Hippel Lindau/hypoxia-inducible factor pathway. Non–clear cell RCC represents a more heterogeneous group of tumors with diverse histopathologic and molecular features. In the past two decades, the improved understanding of the molecular landscape of RCC has led to the development of more effective therapies for metastatic RCC, which include both targeted agents and immune checkpoint inhibitors. Because only subsets of patients with metastatic RCC respond to a given treatment, predictive biomarkers are needed to guide treatment selection and sequence. In this review, we describe the key histologic features and molecular alterations of RCC subtypes and discuss emerging tissue-based biomarkers of response to currently available therapies for metastatic disease.

scholarly journals The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice

2019 ◽  
Vol 20 (17) ◽  
pp. 4263 ◽  
Author(s):  
Alessandra Raimondi ◽  
Giovanni Randon ◽  
Pierangela Sepe ◽  
Melanie Claps ◽  
Elena Verzoni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Practice ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Death Receptor ◽  
Response Assessment ◽  
Disease Response

Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC.

The change of serum C-reactive protein levels during molecular-targeted treatments could predict the response to anti-PD-1 treatment in metastatic renal cell carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17085-e17085
Author(s):  
Kimiharu Takamatsu ◽  
Ryuichi Mizuno ◽  
Nozomi Hayakawa ◽  
Nobuyuki Tanaka ◽  
Takeo Kosaka ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Programmed Death ◽  
Targeted Treatments ◽  
Serum Crp

e17085 Background: Immuno-oncology (IO) checkpoint inhibitors, such as programmed death-1/programmed death-ligand1 (PD-1/PD-L1) inhibitors have been standard of care in the metastatic renal cell carcinoma (mRCC) systemic treatment. However, predictive biomarkers for IO checkpoint inhibitors which is clinically usable have been still unclear. The aim of this study was to evaluate the clinical significance of the change of serum C-reactive protein (CRP) levels during molecular-targeted treatments (VEGFR-TKI and mTOR-I) prior to nivolumab as the predictive marker for the response of nivolumab in patients with refractory mRCC. Methods: A total of 73 mRCC patients (favorable 25(34%), Intermediate 38(52%) and poor 10(14%) risk group by IMDC criteria) treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. The elevation of serum CRP during molecular-targeted therapies before nivolumab induction was defined as the CRP-elevation group. The clinical impact of CRP-elevation as well as other clinical and pathological prognostic factors on progression-free survival (PFS) and overall survival (OS) from nivolumab were assessed. Results: The median follow-up period after nivolumab initiation was 13.2 months (range 3.0-60.8). Forty-nine patients (67%) were categorized into the CRP-elevation group. A clear impact of the CRP-elevation on the response of nivolumab was observed: the median PFS of the CRP-elevation group was 11.9 months, and that of the CRP-non elevation was not-reached (p = 0.038). On multivariate analysis, the CRP-elevation before nivolumab was the independent prognostic factor to predict PFS in nivolumab treatment (HR: 2.68, 95% CI: 1.01-7.11, p = 0.047). CRP-elevation group had a tendency of shorter OS than CRP-non elevation group (p = 0.071). Conclusions: The change of serum CRP levels during molecular-targeted therapies could be the predictive factor for the efficacy of nivolumab in mRCC patients.

scholarly journals Treatment of Metastatic Renal Cell Carcinoma: Latest Evidence and Ongoing Challenges

2018 ◽  
Vol 11 ◽  
pp. 117956111876575 ◽  
Author(s):  
Pedro Aguiar ◽  
Tiago Costa de Pádua ◽  
Carmelia Maria Noia Barreto ◽  
Auro del Giglio
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Synergistic Activity ◽  
Antiangiogenic Drugs ◽  
Metastatic Rcc

Recently, the development of antiangiogenic drugs has changed the therapy for metastatic renal cell carcinoma (RCC). As a result, the survival of individuals with advanced RCC has more than doubled. The median overall survival improved from 12 months during the cytokines era to near 30 months with antiangiogenic drugs. In this decade, the advent of immune checkpoint inhibitors showed enthusiastic results and is the new standard of care for patients with metastatic RCC previously treated with antiangiogenic drugs. The combination of immune checkpoint inhibitors plus antiangiogenic drugs may have a synergistic activity. As a result, current studies investigate the combination for treatment-naïve patients. This may potentially change clinical practice. In this article, we will highlight new therapeutic options available and agents or combinations that are being investigated for metastatic RCC.

Combining Radiotherapy with Immunocheckpoint Inhibitors or CAR-T in Renal Cell Carcinoma

2020 ◽  
Vol 21 (4) ◽  
pp. 416-423 ◽  
Author(s):  
Matteo Santoni ◽  
Daniel Y.C. Heng ◽  
Gaetano Aurilio ◽  
Andrea Iozzelli ◽  
Lucilla Servi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Second Life ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Programmed Death ◽  
Car T

Radiotherapy is considered a second life in Renal Cell Carcinoma (RCC) patients, mainly due to the introduction of immune checkpoint inhibitors, such as anti-Programmed-death (PD)-1, alone or in combination with anti-Cytotoxic T-Lymphocyte Antigen (CTLA)-4. Several trials are investigating the efficacy/safety of immune checkpoint inhibitors in sequential or combined strategies with radiotherapy. Chimeric Antigen Receptor (CAR)-T cells therapy as a promising approach in cancer patients has opened the way to novel possibilities of integrating therapies. The identification of biomarkers of tumor response to these combinations represents a challenge in RCC, together with the research for the best partner for immunotherapy in metastatic patients. In this review we illustrated preclinical/clinical data on the integration of radiotherapy with immunocheckpoint inhibitors or CART cells in RCC.

scholarly journals Immune checkpoint inhibitor – antiangiogenic drugs combination in treatment-naïve metastatic clear cell renal cell carcinoma: Why should immunotherapy have all the fun!

2020 ◽  
Vol 5 ◽  
pp. 1-7
Author(s):  
H. S. Darling ◽  
Alok Gupta
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Algorithm ◽  
Unmet Need ◽  
Real Life ◽  
Antiangiogenic Drugs

Clear cell histology is the most common subtype of renal cell carcinoma (RCC). Immune dysregulation and angiogenic pathways are the main drivers of the pathophysiology of RCC. The prognosis of metastatic RCC has very steadily improved from the era of interferon-alpha to tyrosine kinase inhibitors (TKIs) and then with immune checkpoint inhibitors (IOs). The safety and efficacy of both TKIs and IOs as well as the dire unmet need of further improvement in survival has unfolded the feasibility of successful conduction of IO based combination therapy trials. This has led to the approval of IO-IO and IO-TKI combinations, altering the treatment algorithm altogether once again. In this review, we are trying to look at the robustness of IO–antiangiogenic drugs combination data in upfront setting and its real-life application.

The clinical outcome of renal cell carcinoma with rhabdoid and sarcomatoid differentiation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16083-e16083 ◽  
Author(s):  
Arash Samiei ◽  
Pritam Tayshetye ◽  
Angela Sanguino ◽  
Ralph Miller ◽  
John Lyne ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Survival Data ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Female Ratio ◽  
Pathologic Features ◽  
Mixed Features ◽  
Sarcomatoid Differentiation

e16083 Background: Renal cell carcinoma (RCC) with rhabdoid (RD) or sarcomatoid differentiation (SD) represents high-grade RCC with an aggressive clinical behavior. Little success has been reported in treating these patients. No standard management has been established and there is a lack of insight in these entities because of their relatively low incidences. We reviewed a cohort of RCC patients with RD and SD and correlated the pathologic features with their clinical outcomes. Methods: A retrospective study of RCC patients with RD or SD feature at a single center from 2008 to 2016 was conducted. Patient characteristics, pathology findings, clinical management, and survival data were collected. Results: A total of 36 RCC patients, with median age of 65 [47-88] years old, were included. The male-to-female ratio was 2.6:1. Among them, 24 were with pure SD and 12 with RD (7 pure and 5 mixed features). At diagnosis, 14 patients (38.9%) presented with stage IV disease. The median follow-up was 21 [2-53] months. Of the 36 patients, 24 developed metastasis, including 16/24 (67%) with SD, 4/7 patients (57%) with pure RD, and 4/5(80%) with mixed features. Mortality rate was 79% for SD, 75% for RD and 100% for those with mixed features. The overall survival was 23, 22, and 13 months for SD, pure RD and those with mixed features, respectively. 12 patients were treated with tyrosine kinase inhibitors (TKI) in first-line and 7 with immune checkpoint inhibitors (ICI) in the second or third line setting. Longer duration of treatment was seen with ICI than TKI, 12.8 [5-25] vs 5.9 [1-18] months (p = 0.03). Partial response was seen in 6/7 (86%) and stable disease in 1/7 (14%) patients treated with ICI. No survival benefit was seen in patients treated with TKI alone (p = 0.60). Patients received ICI had significantly prolonged overall survival compared to those received TKI alone, 31.4 vs 17.8 months (p < 0.001). Conclusions: The presence of RD or SD portends poor outcome in RCC with conventional management, especially in those with mix of both features. However, these patients had exceptionally high response and improved survival if treated with ICI. A prospective study using ICI focusing on RCC patients with these pathologic features is warranted and could provide hope for such dismal entities.

1103: Long-Term Survival Following Nephrectomy for Renal Cell Carcinoma: The 15 Year UCLA Experience

2006 ◽  
Vol 175 (4S) ◽  
pp. 355-355
Author(s):  
Manuel Eisenberg ◽  
John S. Lam ◽  
Rakhee H. Goel ◽  
Allan J. Pantuck ◽  
Robert A. Figlin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Term Survival ◽  
Long Term Survival

Adjuvant Therapy in Renal Cell Carcinoma: Current Stance and Future Directions

Kidney Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Austin G. Kazarian ◽  
Neal S. Chawla ◽  
Ramya Muddasani ◽  
Sumanta K. Pal
Keyword(s):  
Renal Cell Carcinoma ◽  
Adjuvant Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Disease Free Survival ◽  
Adjuvant Setting ◽  
Metastatic Setting

In recent years, incredible progress has been made in the treatment of metastatic renal cell carcinoma, with a paradigm shift from the use of cytokines to tyrosine kinase inhibitors, and more recently, immune checkpoint inhibitors (ICIs). Despite advances in the metastatic setting, effective therapies in the adjuvant setting are a largely unmet need. Currently, sunitinib (Sutent, Pfizer) is the only therapy for the adjuvant treatment of RCC included in the National Comprehensive Cancer Network guidelines, which was approved by the FDA based on the improvement in disease-free survival (DFS) seen in the S-TRAC trial. However, improvement in DFS has not translated into an overall survival (OS) benefit for patients at high-risk of relapse post-nephrectomy, illustrating the need for more effective therapies. This manuscript will highlight attributes of both historical and current drug trials and their implications on the landscape of adjuvant therapy. Additionally, we will outline strategies for selecting patients in whom treatment would be most beneficial, as optimal patient selection is a crucial step towards improving outcomes in the adjuvant setting. This is especially critical, given the financial cost and pharmacological toxicity of therapeutic agents. Furthermore, we will review the design of clinical trials including the value of utilizing OS as an endpoint over DFS. Finally, we will discuss how the incorporation of genomic data into predictive models, the use of more sensitive imaging modalities for more accurate staging, and more extensive surgical intervention involving lymph node dissection, may impact outcomes.

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