scholarly journals Immune checkpoint inhibitors in genitourinary malignancies

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
M. Thana ◽  
L. Wood
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Current Evidence ◽  
Testicular Germ Cell ◽  
Testicular Germ Cell Tumours

Although immune-mediated therapies have been used in genitourinary (gu) malignancies for decades, recent advances with monoclonal antibody checkpoint inhibitors (cpis) have led to a number of promising treatment options. In renal cell carcinoma (rcc), cpis have been shown to have benefit over conventional therapies in a number of settings, and they are the standard of care for many patients with metastatic disease. Based on recent data, combinations of cpis and antiangiogenic therapies are likely to become a new standard approach in rcc. In urothelial carcinoma, cpis have been shown to have a role in the second-line treatment of metastatic disease, and a number of clinical trials are actively investigating cpis for other indications. In other gu malignancies, such as prostate cancer, results to date have been less promising. Immunotherapies continue to be an area of active study for all gu disease sites, with several clinical trials ongoing. In this review, we summarize the current evidence for cpi use in rcc, urothelial carcinoma, prostate cancer, testicular germ-cell tumours, and penile carcinoma. Ongoing clinical trials of interest are highlighted, as are the challenges that clinicians and patients will potentially face as immune cpis become a prominent feature in the treatment of gu cancers.

Updates in the management and future landscape of urothelial carcinoma

2020 ◽  
pp. 107815522097102
Author(s):  
Kirollos S Hanna ◽  
Maren Campbell ◽  
Adam Kolling ◽  
Alex Husak ◽  
Sabrina Sturm ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Locally Advanced ◽  
The United States ◽  
Cancer Type ◽  
Antibody Drug Conjugate ◽  
Early Stage Disease

Urothelial carcinoma is the sixth most common cancer type in the United States. Although most patients present with early stage disease which is associated with improved outcomes, many will progress to locally advanced or metastatic disease. Immune checkpoint inhibitors have significantly impacted the treatment paradigm for patients and have resulted in improved survival rates. Despite their proven efficacy, many ongoing clinical trials continue to refine combinations with chemotherapy, sequencing of therapies and the role of ligand expression. Additionally, novel targets have been identified for advanced urothelial carcinoma and have led to the approval of the antibody-drug conjugate, enfortumab vedotin, and the fibroblast growth factor receptor-targeted, erdafitinib. Enrollment in a clinical trial is strongly encouraged for all stages of advanced or metastatic disease. Numerous ongoing clinical trials are likely to impact the treatment armamentarium for patients. In this manuscript, we highlight key updates in the clinical management for patients and outline ongoing trials.

scholarly journals Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5517
Author(s):  
Sara Elena Rebuzzi ◽  
Giuseppe Luigi Banna ◽  
Veronica Murianni ◽  
Alessandra Damassi ◽  
Emilio Francesco Giunta ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Current Evidence ◽  
Concomitant Medications ◽  
Advanced Urothelial Carcinoma

In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients’ characteristics.

scholarly journals Update on the Treatment of Metastatic Urothelial Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Nedal Bukhari ◽  
Humaid O. Al-Shamsi ◽  
Faisal Azam
Keyword(s):  
Clinical Trials ◽  
Urothelial Carcinoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
Line Treatment ◽  
First Line ◽  
Metastatic Urothelial Carcinoma ◽  
Unfit Patients ◽  
Review Reports ◽  
First Line Treatment

Platinum-based combination chemotherapy has been the standard of care in the first-line treatment of metastatic urothelial carcinoma (mUC). Treatment of metastatic disease following progression on platinum-based regimens has evolved significantly in the last few years. Clinical trials are currently ongoing to determine how best to use and sequence these treatments. In this minireview, we will review current first-line treatment options in both cisplatin fit and cisplatin unfit patients and advances in first- and second-line treatments including chemotherapy and immunotherapy. This review reports key findings from the clinical trials especially highlighting the importance of PD-1 and PD-L1 inhibitors in the treatment of bladder/urothelial carcinomas.

Updates and novel treatments in urothelial carcinoma

2018 ◽  
Vol 25 (3) ◽  
pp. 648-656 ◽  
Author(s):  
Kirollos S Hanna
Keyword(s):  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
New Paradigm ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive ◽  
Dose Dense ◽  
Gemcitabine And Cisplatin

Urothelial Carcinoma (UC) is the second most common malignancy of the genitourinary system and is the sixth most common cancer in the USA. Over a decade prior to 2016, the standard of care for early disease consisted of transuretheral resection of the bladder tumor with or without intravesicular chemotherapy or immunotherapy. Systemic chemotherapies such as gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, cisplatin were reserved for recurrent, muscle-invasive, advanced or metastatic disease. Novel treatment approaches for UC have significantly impacted the management of patients. In 2016–2017, five immune checkpoint inhibitors marked a new paradigm in the treatment of UC for patients with advanced or metastatic disease or who are unable to tolerate platinum-based chemotherapy. Most recently, the U.S. Food and Drug Administration set restrictions on two commonly utilized checkpoint inhibitors, atezolizumab and pembrolizumab, in the first-line setting in patients with UC due to decreased survival associated with low expression of the protein programmed death ligand 1. Furthermore, Breakthrough Therapy Designations have been granted for enfortumab vedotin and erdafitinib for patients following platinum-based chemotherapy and those with fibroblast growth factor receptor mutated UC, respectively. Additional updates include dose-dense gemcitabine and cisplatin for muscle-invasive bladder cancer and preoperative checkpoint blockade. This article will review the available data on updates in the treatment of UC and future direction of therapies.

scholarly journals Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3708
Author(s):  
Bhaba K. Das ◽  
Aarthi Kannan ◽  
Quy Nguyen ◽  
Jyoti Gogoi ◽  
Haibo Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Aurora Kinase ◽  
Selective Inhibition ◽  
Potential Candidate ◽  
Cycle Arrest

Merkel cell carcinoma (MCC) is an often-lethal skin cancer with increasing incidence and limited treatment options. Although immune checkpoint inhibitors (ICI) have become the standard of care in advanced MCC, 50% of all MCC patients are ineligible for ICIs, and amongst those treated, many patients develop resistance. There is no therapeutic alternative for these patients, highlighting the urgent clinical need for alternative therapeutic strategies. Using patient-derived genetic insights and data generated in our lab, we identified aurora kinase as a promising therapeutic target for MCC. In this study, we examined the efficacy of the recently developed and highly selective AURKA inhibitor, AK-01 (LY3295668), in six patient-derived MCC cell lines and two MCC cell-line-derived xenograft mouse models. We found that AK-01 potently suppresses MCC survival through apoptosis and cell cycle arrest, particularly in MCPyV-negative MCC cells without RB expression. Despite the challenge posed by its short in vivo durability upon discontinuation, the swift and substantial tumor suppression with low toxicity makes AK-01 a strong potential candidate for MCC management, particularly in combination with existing regimens.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

The evolution of the education module for men with metastatic prostate cancer (mPC) in the prostate cancer supportive care (PCSC) program.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 279-279
Author(s):  
Jennifer Marie Rauw ◽  
Sunil Parimi ◽  
Nikita Ivanov ◽  
Jessica Noble ◽  
Eugenia Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Standard Of Care ◽  
Primary Therapy ◽  
Oncology Nurse ◽  
Castration Resistant ◽  
Medical Oncologists ◽  
Hormone Sensitive ◽  
Virtual Platform ◽  
Satisfaction Surveys

279 Background: The PCSC Program was initiated in 2013 at the Vancouver Prostate Centre to provide a comprehensive program for patients and partners with prostate cancer. This program provides educational sessions (ES) and clinical services, including decision-making for primary therapy, sexual health, pelvic floor physiotherapy, hormone therapy, counseling, exercise, and nutrition for patients in BC, Canada. In 2016, the PCSC Program expanded to BC Cancer Victoria and in 2017 to other BC Cancer sites. In 2018, medical oncologists (MDs) in Victoria (JR, SP) developed an Education Module addressing treatment options for men with metastatic hormone sensitive (mHSPC) and metastatic castration resistant (mCRPC) disease. MDs delivered in-person ES in Victoria in 2018 and, in 2019, added a virtual platform (VP) option. From 3-5/2020, the ESs were on hold due to the COVID pandemic and parental leaves. In 6/2020, the ESs resumed only on VP, and the PCSC Oncology Nurse Practitioner (NP), NI, gave the presentations for the MDs on leave. In 10/2020, due to a changing standard of care for mHSPC, the PCSC team consolidated the two ESs into one. We report on the evolution of this Education Module in response to both the changing standard of care and the COVID pandemic. Methods: We prospectively collected attendance and patient characteristic metrics from all ES for men with mPC. We tracked presenter type (MD vs. NP) and prospectively collected anonymous patient satisfaction questionnaires. Results: From 1/2018 to 1/2021, 100 men registered for 27 ES; 81 men, 41 partners, and 2 family members actually attended. 48/75 (64%) men were white, 39/75 (52%) retired, and 56/75 (74.7%) married. 47 men attended 12 mHSPC ES, 13 men attended ten mCRPC ES, and 17 attended four consolidated ES. MDs presented 15 ES, and the NP presented 12 ES. Responses to questions on 70 satisfaction surveys were similar for MD vs. NP presenters. 9 responders to the recently added VP-specific questions said they agreed (4) or strongly agreed (5) that it was beneficial to watch the ES at home on a computer. The Table below shows attendance per site per year. Conclusions: The ESs for men with mPC were well-received. Although there was a VP option before COVID, attendance increased significantly after the lockdown as patients and providers became more familiar with VPs. Satisfaction surveys confirmed that an NP could deliver the ES rather than MD. Consolidation of the mHSPC and mCRPC ES reflected the changing standard of care and resulted in more efficient use of presenter time. Virtual delivery of the sessions provided greater access to those living in distant or remote areas of the province and those in lockdown during the COVID pandemic. [Table: see text]

scholarly journals New drug developments in metastatic gastric cancer

2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
Author(s):  
Aaron C. Tan ◽  
David L. Chan ◽  
Wasek Faisal ◽  
Nick Pavlakis
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
New Era

Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

scholarly journals Analysis of Clinical Trials on Therapies for Prostate Cancer in Mainland China and Globally from 2010 to 2020

2021 ◽  
Vol 11 ◽  
Author(s):  
Kun Chen ◽  
Kehua Jiang ◽  
Lannan Tang ◽  
Xiaolong Chen ◽  
Jianxin Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Drug Targets ◽  
Checkpoint Inhibitors ◽  
Mainland China ◽  
World Population ◽  
Large Patient ◽  
Future Direction ◽  
Long Acting ◽  
Targeted Chemotherapeutics

The overall aging of the world population has contributed to the continuous upward trend in the incidence of prostate cancer (PC). Trials on PC therapy have been extensively performed, but no study has analyzed the overall trends and characteristics of these trials, especially for those carried out in China. This study aimed to provide insights on the future direction of drug development in PC, thus supplying essential supportive data for stakeholders, including researchers, patients, investors, clinicians, and pharmaceutical industry. The details of the clinical trials of drug therapies for PC during January 1, 2010, to January 1, 2020, were collected from Pharmaprojects. A total of 463 clinical trials on different therapies with 132 different drugs were completed. The long-acting endocrine therapy with few side effects, radiotherapy combined with immune checkpoint inhibitors, gene-targeted chemotherapeutics, and novel immunotherapeutic products changed the concept of PC treatment. In mainland China, 31 trials with 19 drugs have been completed in the 10 assessment years. China has initiated a few trials investigating a limited number of drug targets, centered in a markedly uneven geographical distribution of leading clinical trial units; hence, the development of PC drugs has a long way to go. Given the large patient pool, China deserves widespread attention for PC drug research and development. These findings might have a significant impact on scientific research and industrial investment.

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