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

The treatment landscape for relapsed multiple myeloma has expanded considerably in recent years, as numerous agents with new mechanisms of action have been introduced, increasing responses even in advanced disease and prolonging survival. The wealth of novel regimens comes with the challenges of balancing toxicities and aligning a regimen with the biology of the myeloma and the nature of the relapse in conjunction with patient treatment history and personal preference. Herein, we provide an overview of treatment options for both early and late relapsing disease as well as a discussion of the role of emerging immune-based therapies.

Despite notable screening, diagnostic, and therapeutic advances, disparities in prostate cancer incidence and outcomes remain prevalent. Although commonly discussed in the context of men of African descent, disparities also exist based on socioeconomic level, education level, and geographic location. The factors in these disparities span systemic access issues affecting availability of care, provider awareness, and personal patient views and mistrust. In this review, we will discuss common themes that patients have noted as impediments to care. We will review how equitable access to care has helped improve outcomes among many different groups of patients, including those with local disease and those with metastatic castration-resistant prostate cancer. Even with more advanced presentation, challenges with recommended screening, and lower rates of genomic testing and trial inclusion, Black populations have benefited greatly from various modalities of therapy, achieving comparable and at times superior outcomes with certain types of immunotherapy, chemotherapy, androgen receptor-based inhibitors, and radiopharmaceuticals in advanced disease. We will also briefly discuss access to genomic testing and differences in patterns of gene expression among Black patients and other groups that are traditionally underrepresented in trials and genomic cohort studies. We propose several strategies on behalf of providers and institutions to help promote more equitable care access environments and continued decreases in prostate cancer disparities across many subgroups.

Disparities in health care have an adverse effect on the outcome of disadvantaged patients with cancer. Patients may be at a disadvantage because of geographic isolation; insurance status; or racial, ethnic, or other factors. In this article, we examine how disparities affect the care of patients with sarcoma in the United States, Canada, and the Asia-Pacific region. Because of the rarity of sarcomas and their challenging diagnosis and complex treatment patterns, some professional or national guidelines stipulate that patients with sarcoma should be treated at centers of expertise by multidisciplinary teams. This recommendation, based on published evidence, is not always applicable because of various sociopolitical or patient-related factors. We are proposing solutions to overcome these obstacles in a practical and patient-centered way while acknowledging that disparities exist among countries as well as within any country.

Cervical cancer is a socially and scientifically distinguishable disease. Its pathogenesis, sexual transmission of high-risk HPV to a metaplastic portion of the uterine cervix, makes cervical cancer preventable by safe and effective HPV vaccines commercially available since 2006. Despite this, cervical cancer remains the deadliest gynecologic cancer in the world. Regrettably, global incidence and mortality rates disproportionately affect populations where women are marginalized, where HIV infection is endemic, and where access to preventive vaccination and screening for preinvasive disease are limited. In the United States, cervical cancer incidence has gradually declined over the last 25 years, but mortality rates remain both constant and disparately higher among communities of color because of the adverse roles that racism and poverty play in outcome. Until these conditions improve and widespread prevention is possible, treatment innovations are warranted. The last standard-of-care treatment changes occurred in 1999 for locally advanced disease and in 2014 for metastatic and recurrent disease. The viral and immunologic nature of HPV-induced cervical cancer creates opportunities for both radiation and immunotherapy to improve outcomes. With the advent of T cell-directed therapy, immune checkpoint inhibition, and techniques to increase the therapeutic window of radiation treatment, an overdue wave of innovation is currently emerging in cervical cancer treatment. The purpose of this review is to describe the contemporary developmental therapeutic landscape for cervical cancer that applies to most tumors and to discuss notable rare histologic subtypes that will not be adequately addressed with these treatment innovations.

To realize the full potential of promising new anticancer drugs, it is of paramount importance to administer them at the right dose. The aim of this educational article is to provide several opportunities to optimize anticancer drug dosing, focusing on oral targeted therapies. First, therapeutic drug monitoring can optimize exposure in individual patients, if the optimal concentration is known. This approach is of particular interest in regard to oral kinase inhibitors with high interindividual pharmacokinetic variability. If exposure is related to response, then therapeutic drug monitoring is potentially feasible, although the clinical utility of this approach has not yet been established. Other approaches to reduce variability include administration of more frequent, smaller doses and administration under optimal prandial conditions. However, for many drugs, the labeled dose has not been demonstrated to be the optimal dose; for such agents, the vast majority of patients may be receiving excessive doses, which results in excessive toxicity. Furthermore, administration of lower off-label doses may reduce both medical and financial toxicity. These strategies should be applied from registration studies to clinical practice, with the goal of better optimizing anticancer treatment.

The introduction of novel targeted agents and immunotherapeutic modalities into the treatment of B-cell lymphomas has drastically shifted the treatment landscape. In diffuse large B-cell lymphoma, recent approvals of CAR T-cell therapy, the antibody-drug conjugate polatuzumab, and the anti-CD19 monoclonal antibody tafasitamab have provided efficacious options for patients with relapsed and refractory disease. These immunotherapies attempt to harness power from the patient's own immune system to eradicate lymphoma. In chronic lymphocytic leukemia, oral targeted kinase inhibitors such as ibrutinib and acalabrutinib (Bruton tyrosine kinase inhibitors) and venetoclax (BCL2 inhibitor) are now favored over chemoimmunotherapy for upfront treatment because of improved progression-free survival across all subgroups (including high-risk subgroups such as unmutated immunoglobulin variable heavy chain and chromosome 17p deletion). In indolent lymphomas, several PI3K inhibitors are approved for treatment of relapsed disease. However, uptake of these agents has been limited because of toxicity concerns. Combination of lenalidomide and rituximab has been a safe and effective immune modality for patients with refractory indolent lymphomas; it is currently being used as a backbone to bring other targeted agents such as tazemetostat (EZH2 inhibitor) into earlier lines of treatment. In this article, we will review novel commercially available agents in the treatment of relapsed/refractory diffuse large B-cell lymphoma, treatment-naïve chronic lymphocytic leukemia, and relapsed/refractory indolent lymphomas. We will evaluate clinical trials that led to their approval and will provide an outlook into the future novel agents currently under investigation in B-cell malignancies.

Esophagogastric cancer is associated with rising incidence and high mortality. Nearly 40% of patients have metastatic disease at the time of diagnosis with poor 5-year overall survival. The treatment of squamous cell carcinoma of the esophagus and gastroesophageal adenocarcinoma has started to bifurcate in recent years, owing to the evolving understanding of the biologic and genomic characteristics of these tumors. Incorporation of HER2-directed therapy in the form of monoclonal antibody and antibody-drug conjugate is now standard of care for patients with HER2-positive disease. The addition of immune checkpoint inhibitors to the therapeutic landscape of metastatic esophagogastric cancer is associated with modest improvement in overall survival, and definition of predictive biomarkers of response to checkpoint inhibition remains imprecise. A number of therapeutic targets including FGFR2b, Claudin 18.2, DKK-1, and DNA repair defects are being explored in clinical trials. Similarly, combination immunotherapy and novel HER2-targeting agents, such as bispecific antibody and small-molecule inhibitors, are at various stages of clinical development. Despite the progress made in the field of targeted therapies and checkpoint inhibition, chemotherapy remains an integral part of treatment of metastatic esophagogastric cancer but is associated with considerable toxicity. Clinical trials focusing on minimizing toxicity of currently available therapeutic agents, development of novel biomarker-driven treatment strategies, and overcoming resistance to immune checkpoint inhibition will define the future of this traditionally indelible disease.

Systemic therapy for first-line metastatic renal cell carcinoma has evolved toward immune checkpoint blockade combinations incorporating a PD-1/L1 inhibitor along with CTLA-4 inhibition or VEGF-targeted therapy. The new treatment paradigm that integrates immunotherapy for treatment-naïve advanced metastatic renal cell carcinoma creates a new therapeutic challenge for clinicians including the optimal way to integrate multidisciplinary care involving surgery, radiotherapy, and application of contemporaneous systemic treatment in subsequent lines of therapy following discontinuation of combination therapy. We outline the available data for the multidisciplinary management of metastatic renal cell carcinoma, systemic therapy options in the post-immune checkpoint blockade setting, and novel therapies in development for advanced renal cell carcinoma. We provide practical considerations to assist clinicians in treatment choice and map future directions for progress.

The treatment paradigm for patients with advanced non-small cell lung cancer has substantially changed with the discovery of immunotherapy. The incorporation of immunotherapy into treatment algorithms has resulted in better outcomes for patients, with fewer side effects compared with classic chemotherapeutic agents. Multiple treatment options are now available for patients with advanced non-small cell lung cancer, ranging from single-agent immunotherapy to quadruple therapy, which involves dual immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor plus chemotherapy plus anti-vascular endothelial growth factor drugs. This article will review landmark studies that have led to U.S. Food and Drug Administration approval of immunotherapy agents alone or in combination with chemotherapy or other immunotherapy drugs to treat advanced non-small cell lung cancer.

Adoptive cell therapy has significantly impacted the immuno-oncology landscape. The number of strategies currently in preclinical and clinical development is increasing at a rapid rate. Indeed, we are experiencing a transformative movement in cancer care as we shift toward highly personalized treatments designed to confront the specific challenges of each cancer. Advancements in genetic engineering methods and single-cell profiling technologies provide a level of understanding of the interactions between the immune system and cancer never before achieved. This knowledge, in turn, can be applied to the design and engineering of effective cancer-fighting treatments. As these promising new therapies progress toward clinical application, it becomes evident that we must develop robust methods for production and validation of cellular products to ensure consistency, safety, and efficacy, irrespective of cell type or indication. Herein, we provide an overview of the innovative approaches guiding the new generation of cell therapies and describe the benefits and challenges associated with emerging autologous and allogeneic platforms. Moreover, we discuss important considerations pertaining to process development, cost of goods, and manufacturing, and highlight their impact on the transfer of therapies from bench to bedside.