scholarly journals The Year in Review for Renal Cancer

2020 ◽  
Vol 7 (1) ◽  
pp. 5-6
Author(s):  
Ulka Vaishampayan
Keyword(s):  
Renal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Front Line ◽  
Advanced Renal Cancer ◽  
Fda Approval ◽  
Multiple Biomarkers ◽  
Line Setting

The treatment of kidney cancer has made some remarkable strides over the last few years. Two regimens received Food and Drug Administration (FDA) approval, multiple biomarkers were reported to show promise, and further enhancement and refinement of the prognostic characteristics occurred. The combinations of anti-angiogenic tyrosine kinase inhibitors with immune checkpoint inhibitors have rap-idly become the preferred therapies in the front-line setting of advanced renal cancer.

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

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Revati Sharma ◽  
Elif Kadife ◽  
Mark Myers ◽  
George Kannourakis ◽  
Prashanth Prithviraj ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Resistance Mechanisms ◽  
Number Of Patients ◽  
Angiogenesis Pathway

AbstractVascular 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.

scholarly journals Immune Checkpoint Inhibitors as Monotherapy or Within a Combinatorial Strategy in Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 21 (17) ◽  
pp. 6302
Author(s):  
Michela Guardascione ◽  
Giuseppe Toffoli
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Antiangiogenic Agents ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

In advanced-stage hepatocellular carcinoma (HCC), systemic treatment represents the standard therapy. Target therapy has marked a new era based on a greater knowledge of molecular disease signaling. Nonetheless, survival outcomes and long-term response remain unsatisfactory, mostly because of the onset of primary or acquired resistance. More recently, results from clinical trials with immune targeting agents, such as the immune checkpoint inhibitors (ICIs), have shown a promising role for these drugs in the treatment of advanced HCC. In the context of an intrinsic tolerogenic liver environment, since HCC-induced immune tolerance, it is supported by multiple immunosuppressive mechanisms and several clinical trials are now underway to evaluate ICI-based combinations, including their associations with antiangiogenic agents or multikinase kinase inhibitors and multiple ICIs combinations. In this review, we will first discuss the basic principles of hepatic immunogenic tolerance and the evasive mechanism of antitumor immunity in HCC; furthermore we will elucidate the consistent biological rationale for immunotherapy in HCC even in the presence of an intrinsic tolerogenic environment. Subsequently, we will critically report and discuss current literature on ICIs in the treatment of advanced HCC, including a focus on the currently explored combinatorial strategies and their rationales. Finally, we will consider both challenges and future directions in this field.

scholarly journals Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 738 ◽  
Author(s):  
Raju K. Vaddepally ◽  
Prakash Kharel ◽  
Ramesh Pandey ◽  
Rohan Garje ◽  
Abhinav B. Chandra
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Hematopoietic Cells ◽  
Fda Approval ◽  
Programmed Death ◽  
Cancerous Cells

Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.

scholarly journals Immune checkpoint inhibitors in renal cell carcinoma

2017 ◽  
Vol 131 (21) ◽  
pp. 2627-2642 ◽  
Author(s):  
Kirsty Ross ◽  
Rob J. Jones
Keyword(s):  
Renal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Optimal Timing ◽  
New Class ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Immune Manipulation

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.

scholarly journals Transarterial Chemoembolization Improves Survival in Advanced Hepatocellular Carcinoma Patients Treated with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors

2021 ◽  
Author(s):  
Yue Hu ◽  
Tao Pan ◽  
Xi Cai ◽  
Quansheng He ◽  
Yubao Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Immune Checkpoint ◽  
Transarterial Chemoembolization ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Tace Group

Abstract BackgroundThe survival benefit and safety of transarterial chemoembolization (TACE) for advanced Hepatocellular Carcinoma (HCC) patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) is unclear. We aimed to investigate the efficacy and safety of TACE combined with TKIs and ICIs the treatment of advanced HCC. MethodsIn this study, the conditions of 147 patients with advanced HCC who underwent TKIs plus ICIs treatment between July 2017 and April 2020 were evaluated. We divided these patients into the TACE group and non-TACE group based on whether they were treated with TACE during TKIs plus ICIs treatment, and compared their survival outcomes, especially overall survival (OS), and whether they were exposed to unexpected toxicities. ResultsIn this study, a total of 98 patients who underwent TACE during TKIs plus ICIs treatment were included in the TACE group, while the other 49 patients were included in the non-TACE group. According to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST), the objective response rate (ORR) of the TACE group was higher than that of the non-TACE group (ORR 74.5% vs. 40.8%, p ＜0.001). The OS of the TACE group was significantly longer than the non-TACE group (OS 19.3 months vs. 10.8 months, p = 0.010). The incidence of grade 3-4 toxicities in the TACE group was similar to that in the non-TACE group (33.7% vs. 28.6%, p = 0.532). ConclusionsThe TACE treatment combined with TKIs plus ICIs resulted in longer OS compared to the treatment of systemic TKIs plus ICIs without TACE during the process of advanced HCC.

scholarly journals The New Immuno-Oncology-Based Therapies and Their Perspectives in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 238
Author(s):  
Philippe Merle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Complete Response ◽  
Phase 3 ◽  
Long Survival ◽  
Systemic Therapies

Hepatocellular carcinoma is a poor prognosis tumor. Systemic therapies are frequently used due to frequent recurrences after surgical or radiologic treatments. Anti-angiogenic tyrosine kinase inhibitors have shown efficacy in monotherapy, but with very low rates of long survival and exceptional recovery. Immuno-oncology based on immune checkpoint inhibitors has revolutionized the systemic therapies since showing long survival rates without any tumor progression or recurrence for some patients in partial or complete response, and possibly for some patients in stable disease. However, the rate of responders under immuno-oncology monotherapy is too low to increase significantly the median overall survival of the treated patients. The immuno-oncology-based combinations with different types of immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 inhibitors such as nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, tremelimumab), or the association of immune checkpoint inhibitors plus anti-angiogenic agents (bevacizumab, lenvatinib, cabozantinib), have led to a breakthrough in the treatment of hepatocellular carcinoma. Indeed, the first phase-3 trial, combining atezolizumab with bevacizumab, has dramatically changed the outcome of patients. Data from several other types of combinations assessed in phase-3 trials are pending, and if positive, will drastically arm the physicians to efficiently treat the patients, and disrupt the current algorithm of hepatocellular carcinoma treatment.

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