American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting最新文献

{"title":"Update on Biomarkers in Renal Cell Carcinoma.","authors":"Renée M Saliby, Eddy Saad, Soki Kashima, David A Schoenfeld, David A Braun","doi":"10.1200/EDBK_430734","DOIUrl":"10.1200/EDBK_430734","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":"44 2","pages":"e430734"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immuno-Oncology Advances in Genitourinary Cancers.","authors":"Peter D Zang, Arkhjamil Angeles, Tanya B Dorff, Sumanta K Pal, Shilpa Gupta","doi":"10.1200/EDBK_430428","DOIUrl":"10.1200/EDBK_430428","url":null,"abstract":"<p><p>Immuno-oncology (IO) has made monumental gains in the past decade in the genitourinary space. In this review, we highlight advances with IO in renal cell carcinoma where it now has become standard-of-care frontline therapy in the metastatic setting but also discuss challenges with the initial approach. In urothelial carcinoma, we discuss the growing use of IO including exciting recent updates with IO-based regimens that may soon become the new standard of care. We further discuss difficulties with IO in prostate cancer, germ cell tumors, and penile squamous cell carcinoma. Finally, we highlight advances in IO approaches beyond checkpoint inhibition including the role of the gut microbiome and T-cell redirecting therapies.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":"44 2","pages":"e430428"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates on Systemic Therapy for Hepatocellular Carcinoma.","authors":"Panagiotis Ntellas, Ian Chau","doi":"10.1200/EDBK_430028","DOIUrl":"10.1200/EDBK_430028","url":null,"abstract":"<p><p>This review explores the dynamic landscape of hepatocellular carcinoma (HCC) treatment, emphasizing on recent developments across various stages and therapeutic approaches. Although curative strategies such as hepatectomy and thermal ablation are standard for early-stage cases, high relapse rates drive investigations into adjuvant and perioperative treatment. Adjuvant therapies face hurdles, but noteworthy advances include IMbrave050 setting a new standard with atezolizumab/bevacizumab. Locoregional treatments gain significance, especially for multifocal HCC, with the integration of innovative combinations with systemic therapies, showing improved outcomes. In the advanced setting, the evolution from sorafenib as the primary first-line option to new standards, such as atezolizumab/bevacizumab and tremelimumab/durvalumab, to other emerging therapies such as tislelizumab and pembrolizumab with lenvatinib, is explored. Additionally, second-line treatments and insights into the interplay between immunotherapies and antiangiogenic agents, as well as novel combination strategies that add complexity to treatment decisions, are discussed.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":"44 ","pages":"e430028"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Challenges in Access to and Implementation of Precision Oncology: The Health Care Manager and Health Economist Perspective.","authors":"Ya-Chen Tina Shih,&nbsp;I-Wen Pan,&nbsp;Nelson Teich","doi":"10.1200/EDBK_359650","DOIUrl":"https://doi.org/10.1200/EDBK_359650","url":null,"abstract":"<p><p>Precision medicine changes the landscape of oncology practices by offering the opportunity to optimize care through a more targeted, personalized approach of managing cancer treatments. However, precision oncology is costly and does not benefit all patients with cancer, making it critically important to consider the tradeoff between costs and health benefits. Here, we discuss the global challenges in implementing precision oncology from the perspective of health care management and health economics and emphasize the different challenges for high-income compared with low- and middle-income countries. For health care managers making resource allocation decisions, the decision to adopt, implement, and finance precision oncology must consider opportunity costs, and the allocation must be proportional to the system's capacity. The standard approach of health technology assessment is inadequate because it fails to consider the capacity to pay. From an economic perspective, global implementation of precision oncology must confront the issues of accessibility, affordability, and system readiness. Low- and middle-income countries often have no or delayed access to novel targeted-therapy agents, find these drugs cost-prohibitive, and struggle to build the infrastructure with sufficient workforce and adequate testing and computing facilities to capitalize the benefit of precision oncology. Although high-income countries are better equipped to implement precision oncology, the challenges there lie in implementing strategies to maximize the value of precision oncology through promoting appropriate use while limiting inappropriate applications. The recent rollout of COVID-19 vaccines internationally highlights the importance of information uncertainty and offers valuable insights on global access to and implementation of precision oncology.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":" ","pages":"429-437"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40501791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Cancer Priorities in Limited-Resource Environments: The Price-Efficacy Dilemma in Cancer Care.","authors":"Sana Al-Sukhun,&nbsp;Fayez Tbaishat,&nbsp;Nazik Hammad","doi":"10.1200/EDBK_349861","DOIUrl":"https://doi.org/10.1200/EDBK_349861","url":null,"abstract":"Breast cancer has become one of the leading causes of morbidity and mortality in low- and middle-income countries, where 62% of the world's total new cases are diagnosed. Therefore, the productivity loss because of premature death resulting from female breast cancer is also on the rise. The major challenge in low- and middle-income countries is to reduce the proportion of women presenting with advanced-stage disease, a challenge unlikely to be overcome by adoption of expensive national mammography screening programs. Awareness and education campaigns should focus not only on patients and societies but also on policy makers to address and optimize breast cancer care. Adaptation of existing guidelines and prioritization according to local resources are essential to address the unique needs and overcome the unique barriers of each society to facilitate practical implementation and improve outcomes. Emphasis on the principle of a cancer groundshot in addressing value in cancer care is vital to improving access to therapies that are proven to work rather than chasing after new drugs or innovations of doubtful or marginal clinical benefit. Until we have drug-pricing interventions that take into account the local income of each society, we must acknowledge the fact that the delivery of cancer care will never be the same all around the world.","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40194731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Challenges in Access to Melanoma Care: A Multidisciplinary Perspective.","authors":"Nikhil I Khushalani,&nbsp;Thach-Giao Truong,&nbsp;John F Thompson","doi":"10.1200/EDBK_320301","DOIUrl":"https://doi.org/10.1200/EDBK_320301","url":null,"abstract":"<p><p>A diagnosis of melanoma requires multidisciplinary specialized care across all stages of disease. Although many important advances have been made for the treatment of melanoma for local and advanced disease, barriers to optimal care remain for many patients who live in areas without ready access to the expertise of a specialized melanoma center. In this article, we review some of the recent advances in the treatment of melanoma and the persistent challenges around the world that prevent the delivery of the best standard of care to patients living in the community. With the therapeutic landscape continuing to evolve and newer more complex drug therapies soon to be approved, it is important to recognize the many challenges that patients face and attempt to identify tools and policies that will help to improve treatment outcomes for their melanoma.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":" ","pages":"e295-e303"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39037574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tyrosine Kinase Inhibitors, Antibody-Drug Conjugates, and Proteolysis-Targeting Chimeras: The Pharmacology of Cutting-Edge Lung Cancer Therapies.","authors":"Jennifer W Carlisle,&nbsp;R Donald Harvey","doi":"10.1200/EDBK_320667","DOIUrl":"https://doi.org/10.1200/EDBK_320667","url":null,"abstract":"<p><p>The number of therapeutic options available for patients with advanced non-small-cell lung cancer has been led by deeper understanding of molecular drivers, immune function, and fundamental biology. In this article, we describe the relevant clinical pharmacologic characteristics of three broad classes of existing and investigational treatments, with a focus on mechanisms of action, adverse event profiles, pharmacokinetic and pharmacodynamic properties, and known and predicted resistance pathways. Specifically, within the kinase inhibitor class, agents directed against the RET, MET, and KRAS pathways are reviewed. Additionally, the first antibody-drug conjugates that target HER2 and HER3 are in trials and will ideally be available for patients soon. Finally, proteolysis-targeting chimeras approach pathway inhibition through enzyme degradation rather than target inhibition and are a promising platform for new agents in non-small-cell lung cancer and across cancer types. Each of these classes requires knowledge of clinical pharmacologic principles in development and use to ensure patient care in clinics and trials is optimized and personalized, including dosing and scheduling strategies, potential drug interactions, use in special populations, and monitoring parameters. Ideally, oncologists will continue to have new agents available across the non-small-cell lung cancer treatment spectrum to offer to a patient group that, until relatively recently, had few options.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":" ","pages":"e286-e293"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39038979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibition in Advanced Bladder and Kidney Cancer: Responses and Further Management.","authors":"Mamta Parikh,&nbsp;Thomas Powles","doi":"10.1200/EDBK_323835","DOIUrl":"https://doi.org/10.1200/EDBK_323835","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have an established role in the treatment of newly diagnosed metastatic kidney cancer. Treatment regimens combining nivolumab plus ipilimumab, pembrolizumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib have demonstrated superior overall survival compared with sunitinib in randomized studies. Response rates vary from 42% to 71.1% with these combinations. Atezolizumab and pembrolizumab have been approved for the treatment of cisplatin-ineligible patients with metastatic bladder cancer. These and other checkpoint inhibitors have been studied in metastatic bladder cancer and are routinely used after progression on platinum-based chemotherapy. Durable responses are observed in bladder and kidney cancer. Although some patients may experience immune-related adverse events requiring treatment discontinuation, a portion of these patients will continue to experience a response off-therapy. At the time of progression, patients with metastatic kidney cancer may be treated with antiangiogenesis agents, and there are data suggesting that they may also be treated with a rechallenge of immunotherapy. In patients with metastatic bladder cancer who have progression after immune checkpoint inhibition, there are considerable data supporting the use of enfortumab vedotin. Ongoing studies are evaluating novel combinations of immune checkpoint inhibitors with other agents; thus, the treatment landscape of metastatic bladder and kidney cancer is expected to continue to evolve rapidly.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":" ","pages":"e182-e189"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39038978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moving Beyond 3+3: The Future of Clinical Trial Design.","authors":"Razelle Kurzrock,&nbsp;Chia-Chi Lin,&nbsp;Tsung-Che Wu,&nbsp;Brian P Hobbs,&nbsp;Roberto Carmagnani Pestana,&nbsp;David S Hong","doi":"10.1200/EDBK_319783","DOIUrl":"https://doi.org/10.1200/EDBK_319783","url":null,"abstract":"<p><p>Misgivings have been raised about the operating characteristics of the canonical 3+3 dose-escalation phase I clinical trial design. Yet, the traditional 3+3 design is still the most commonly used. Although it has been implied that adhering to this design is due to a stubborn reluctance to adopt change despite other designs performing better in hypothetical computer-generated simulation models, the continued adherence to 3+3 dose-escalation phase I strategies is more likely because these designs perform the best in the real world, pinpointing the correct dose and important side effects with an acceptable degree of precision. Beyond statistical simulations, there are little data to refute the supposed shortcomings ascribed to the 3+3 method. Even so, to address the unique nuances of gene- and immune-targeted compounds, a variety of inventive phase 1 trial designs have been suggested. Strategies for developing these therapies have launched first-in-human studies devised to acquire a breadth of patient data that far exceed the size of a typical phase I design and blur the distinction between dose selection and efficacy evaluation. Recent phase I trials of promising cancer therapies assessed objective tumor response and durability at various doses and schedules as well as incorporated multiple expansion cohorts spanning a variety of histology or biomarker-defined tumor subtypes, sometimes resulting in U.S. Food and Drug Administration approval after phase I. This article reviews recent innovations in phase I design from the perspective of multiple stakeholders and provides recommendations for future trials.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":" ","pages":"e133-e144"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39038983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Androgen Receptor: The Sequence, the Mutants, and New Avengers in the Treatment of Castrate-Resistant Metastatic Prostate Cancer.","authors":"Daniel Westaby,&nbsp;Paul V Viscuse,&nbsp;Rahul Ravilla,&nbsp;Maria de Los Dolores Fenor de la Maza,&nbsp;Andrew Hahn,&nbsp;Adam Sharp,&nbsp;Johann de Bono,&nbsp;Ana Aparicio,&nbsp;Mark T Fleming","doi":"10.1200/EDBK_321209","DOIUrl":"https://doi.org/10.1200/EDBK_321209","url":null,"abstract":"<p><p>Targeting the androgen receptor by depriving testosterone with gonadotropin-releasing hormone agonists or antagonists, or surgical castration, has been the backbone of metastatic prostate cancer treatment. Although most prostate cancers initially respond to androgen deprivation, metastatic castration-resistant prostate cancer evolves into a heterogeneous disease with diverse drivers of progression and mechanisms of therapeutic resistance. Development of castrate resistance phenotype is associated with lethality despite the recent noteworthy strides gained via increase in therapeutic options. Identification of novel therapeutics to further improve survival and achieve durable responses in metastatic castration-resistant prostate cancer is a clinical necessity. In this review, we outline the existing avengers for treatment of metastatic castration-resistant prostate cancer by clinical presentation, placing into context the clinical state of the patient, such as burden of disease and symptoms. Doing so might aid in the ability to optimize the sequence of agents and allow for maximal exposure to life-prolonging therapeutics. Realizing the limitations of the androgen signaling inhibition, we explore the androgen-indifferent prostate cancer: the mutants. Classically, these subtypes have been associated with variant histology, but androgen-indifferent prostate cancer features are now frequently observed in association with heterogeneous morphologies, including double-negative prostate cancers, lacking both androgen receptor and neuroendocrine features, or clinicopathologic criteria, such as the aggressive variant prostate cancer criteria. The framework of new avengers against metastatic castration-resistant prostate cancer based on mechanism, including DNA repair, immune checkpoint inhibition, PTEN/PI3K/AKT pathway, prostate-specific membrane antigen targets, bispecific T-cell engagers, and radionuclide therapies, is summarized in this review.</p>","PeriodicalId":37969,"journal":{"name":"American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting","volume":" ","pages":"e190-e202"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39038981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}