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

Therapeutic advances have resulted in a growing population of childhood cancer survivors. Unfortunately, this success comes at a price. A substantial proportion of the survivors develop life-threatening chronic health conditions such as subsequent neoplasms and cardiovascular diseases. These conditions are likely initiated by exposure to chemotherapy and radiation used to treat the underlying childhood cancer and potentiated by additional accumulation of comorbidities. These conditions can cause premature death, resulting in significantly shorter lifespans. Previous research using large cohorts of childhood cancer survivors has described the magnitude of the burden or morbidity and the association between key therapeutic exposures and specific chronic health conditions. These findings have resulted in the creation of risk-based guidelines for surveillance and early detection of the complications. Now, research is increasingly focused on understanding the pathogenesis of treatment-related complications, identifying survivors at risk for these complications, developing targeted interventions, determining where and how to provide life-long risk-based care, and finally, whether providing risk-based surveillance will mitigate the burden of morbidity and mortality among childhood cancer survivors. We address these topics in this manuscript.

The choice of frontline therapy for a patient with chronic phase chronic myeloid leukemia (CP-CML) can have a profound effect on the long-term clinical outcome. Currently, five tyrosine kinase inhibitors (TKIs-imatinib, dasatinib, nilotinib, bosutinib, and asciminib) are available for frontline therapy, but no single TKI is optimal for all patients. EUTOS long-term survival (ELTS) risk score, comorbidities, and treatment-free remission (TFR) priority are the key determinants of frontline TKI selection. Higher ELTS score, low age and comorbidity score, and a high priority for achievement of TFR would all favor the frontline use of a more potent TKI than imatinib. However, no TKI has improved survival compared with imatinib. In children with CP-CML, imatinib, dasatinib, and nilotinib have similar long-term efficacy, with ease of administration and impact of toxicities on quality of life being key considerations. Recent adult trials of reduced-dose dasatinib frontline showed that efficacy may be equivalent to standard-dose dasatinib with a better tolerability and safety profile, but experience is limited in patients with high-risk ELTS scores. The ASC4FIRST trial has confirmed that tolerability and molecular response with asciminib are superior to those with both imatinib and the second-generation (2G)-TKIs. While the overall treatment failure rate was lower with asciminib, the rate of BCR::ABL1 mutations that emerged with asciminib appeared to be higher. The risk of emergent mutations appears to be highly associated with the presence of ASXL1 mutations in the CML cells at diagnosis, but more work is needed to understand the implications of this finding.

Until recently, the treatment of metastatic castration-resistant prostate cancer (mCRPC) relied exclusively on hormonal therapies and taxane chemotherapy. The advent of modern molecular profiling methods applied in the clinic, namely, next-generation sequencing and advanced positron emission tomography (PET) imaging, has allowed for the development of biomarker-driven therapeutics including anti-PD-L1 therapy for microsatellite instability-high or tumor mutation burden-high disease, poly(ADP-ribose) polymerase (PARP) inhibitors for patients with DNA damage repair mutations, and lutetium 177 vipivotide tetraxetan (¹⁷⁷Lu-PSMA-617) for patients with prostate-specific membrane antigen (PSMA) PET-avid disease. While these targeted therapies have improved outcomes, there is an opportunity to refine biomarkers to optimize patient selection, understand resistance, and develop novel combination strategies. In addition, studies in the laboratory and in patient-derived samples have shown that a subset of mCRPC tumors lose expression of common prostate cancer markers such as prostate-specific antigen and PSMA because of lineage plasticity and the development of non-androgen receptor (AR)-driven disease. Non-AR-driven prostate cancer has been associated with aggressive behavior and poor prognosis, including in some cases histologic transformation to a poorly differentiated neuroendocrine prostate cancer (NEPC). The clinical management of NEPC typically follows the treatment paradigm for small cell lung cancer and increasingly relies on genomic and phenotypic characterization of disease, including loss of tumor suppressors and expression of cell surface markers such as DLL3. Therefore, both genomic subtyping and phenotypic subtyping are important to consider and can guide the clinical management of patients with advanced prostate cancer.

Although there is a growing number of people living with advanced or metastatic cancer, primarily because of more effective treatment regimens, there are limited estimates of the actual number of people living with advanced or metastatic cancer. Many people will have treatable but not curable cancers, may have survival measured in years, and may have periods on and off therapy. People with advanced or metastatic disease, as well as their families and caregivers, may experience significant unmet needs, overlapping yet distinct to those with potentially curable cancer. Recently, the Multinational Association of Supportive Care in Cancer and ASCO developed standards and practice recommendations relevant to the delivery of quality survivorship care for people living with advanced or metastatic cancer. The recommendations included seven domains: (1) person-centered care; (2) coordinated and integrated care; (3) evidence-based and comprehensive care; (4) evaluated and communicated care; (5) accessible and equitable care; (6) sustainable and resourced care; and (7) research and data-driven care. Immediate priorities to improve clinical care include focusing on (1) discussions regarding prognosis and goals of care; (2) routinely assessing physical, psychological, and social unmet needs with referral to appropriate supportive care services; and (3) creating blended models of care, incorporating elements of palliative care and survivorship services. Additional areas for focus include (1) advocacy and policy; (2) system design and health care delivery; (3) defining, measuring, and managing quality; (4) addressing inequity; and (5) research specifically focused on these cancer populations.

Bispecific antibodies (bsAbs) have emerged as a novel class of therapeutics, offering a dual-targeting strategy to enhance the therapeutic efficacy of monoclonal antibodies, which is often limited by tumor heterogeneity and the occurrence of resistance mechanisms. By simultaneously engaging two distinct antigens or pathways, bsAbs disrupt multiple signaling cascades simultaneously, preventing escape mechanisms and offering a more durable response. Furthermore, they can optimize immune activation, improving immune cell recruitment strategies. In particular, T-cell engager bsAbs facilitate immune cell-mediated tumor destruction by linking T cells to tumor antigens. Instead, dual immune checkpoint inhibitors (CPIs) enhance immune activation by blocking inhibitory signals. Additionally, bsAbs targeting tumor growth factors or receptor tyrosine kinases offer solutions for overcoming drug resistance in solid tumors. Although bsAbs have shown remarkable success in hematologic malignancies, their expansion into solid tumors faces key challenges, including tumor heterogeneity, limited tumor penetration, and the risk of on-target, off-tumor toxicities. Addressing these challenges requires innovative engineering strategies, optimized delivery mechanisms, and careful patient selection to maximize therapeutic benefit while mitigating adverse effects. The efficacy of bsAbs in clinical trials has led to their approval for both hematologic and solid malignancies, with numerous agents in development. Combination strategies with chemotherapy, targeted agents, and immune CPIs could represent a promising strategy to further expand their potential. As research progresses, bsAbs are expected to play a role in reshaping the future of precision oncology, offering more effective and tailored treatment options.

Triple-negative breast cancer (TNBC) was first described as a distinct disease entity 20 years ago. Since that time, there has been tremendous effort invested in understanding the clinical features and biology of this breast cancer subtype and developing novel therapeutics specifically targeted for this group of tumors. This review will focus on therapeutic advances in the treatment of metastatic TNBC, outlining successes that contributed to expanded treatment options for advanced TNBC at present and highlight areas of ongoing investigation with potential to further advance treatment paradigms for this aggressive breast cancer subtype. Since 2018, five new therapies have been introduced into clinical practice for the treatment of advanced TNBC. Poly(ADP-ribose) polymerase inhibitors represent the only success for genomically targeted therapy, and this is an option only for a small subgroup of patients with TNBC and a germline BRCA1 or BRCA2 pathogenic variant. Pembrolizumab is currently the only PD-1 checkpoint inhibitor approved in the United States in combination with chemotherapy in the first-line setting and is an option for roughly 40% of patients with PD-L1 positive tumors. Antibody-drug conjugates have been an important advance in the treatment of advanced TNBC, although these drugs do not represent a TNBC-specific advance as both sacituzumab govitecan and trastuzumab deruxtecan have activity in breast tumors beyond TNBC. Thus, despite significant strides over the past decade, significant unmet clinical need persists, and novel therapeutics remain a pressing need for the treatment of advanced TNBC.

Oncology rehabilitation and exercise (ORE) exist along a continuum of care, providing essential services for patients with cancer to improve health outcomes. Although oncology rehabilitation, typically delivered by licensed medical professionals, is often covered by third-party payers, exercise oncology remains largely unfunded despite its strong evidence base. Research indicates that exercise interventions improve cancer-related fatigue, physical function, mental health, and quality of life, yet referral and implementation remain limited. A geospatial analysis highlights disparity in program availability, particularly in rural and underserved areas. Effective ORE programs require systematic planning, institutional support, clinical workflow integration, and sustainable funding. Case analyses suggest that program adoption depends on leadership buy-in, organizational readiness, and structured referral pathways. Implementation science (IS) provides a framework to address real-world barriers, ensuring efficient integration of exercise services into oncology care. Screening and triage models can aid in patient assessment, streamlining referrals to appropriate levels of exercise intervention. Despite growing policy efforts, widespread third-party reimbursement remains elusive. Leveraging IS strategies can facilitate the adoption and sustainability of ORE programs, bridging the gap between research and practice. Future directions should focus on improving clinician education, expanding access through policy initiatives, and integrating exercise interventions into standard oncology care to optimize patient outcomes.

Immunotherapy has significantly affected cancer treatment and survival rates, accompanied by an increase in immune-related adverse events (irAEs) requiring new management strategies. irAEs can affect various organ systems and have varying severity levels, with higher rates observed when combining immune checkpoint inhibitors. National organizations such as ASCO, the National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society for Medical Oncology have created guidelines for managing irAEs. This chapter expands on these guidelines by discussing practical strategies to improve the multidisciplinary management in irAE care, focusing on the who, what, and how to bridge gaps in care and enhance collaboration between academic and community oncology practices. Effective irAE management involves early recognition and guideline-adherent approaches using a multidisciplinary team, including oncologists, other subspecialists, primary care clinicians, and all care team members. Institutions are developing methods to integrate irAE care into clinical workflows, such as incorporating urgent care clinics and e-consults for efficient irAE management and developing hub-and-spoke models to extend specialized care from academic centers to community hospitals for equitable care delivery. Additionally, effective patient education is critical for improving irAE recognition and health literacy. The new ASCO Community of Practice called the Alliance for Support and Prevention of Immune-Related Adverse Events consortium and patient advocacy group Standing Together to Optimize Research, Interventions, and Education in irAEs initiatives aim to advance irAE clinical care, research, and education through global collaboration, standardized data collection, and improved outreach to patients and caregivers.

Hematologic precursor conditions include monoclonal gammopathy of undetermined significance (MGUS), monoclonal B-cell lymphocytosis (MBL), and clonal hematopoiesis (CH). These conditions are characterized by a clonal expansion of either plasma cells, lymphoid cells, or myeloid cells without meeting criteria for active hematologic malignancy and are considered premalignant conditions. Diagnosis of these precursor conditions often occur incidentally based on abnormalities on routine laboratory assessments, such as an elevated globulin level leading to diagnosis of MGUS or smoldering multiple myeloma (SMM) or elevated absolute lymphocyte count on blood count checks leading to MBL identification. Diagnosis of CH requires next-generation sequencing of peripheral blood or bone marrow to identify expansion in somatic genetic alterations in hematopoietic cells. Epidemiologic studies of these precursor conditions show that they are relatively common and increase with age, with prevalence of MGUS of 3%-4% in individuals older than 50 years, 3%-17% in adult populations for MBL, and 10% of individuals older than 50 years for CH. Evaluating the risk of progression to overt disease in an individual with a precursor condition is critical in determining management. Often, the risk of progression is quite low, or the latency period is quite long, and for which observation is the current standard of care among these patients. Various risk stratification systems or calculators have been developed for MGUS/SMM, MBL, and CH to better delineate a patient's risk. There is active clinical investigation regarding the role of early intervention among patients who are at highest risk of progression to active hematologic malignancy.

Pancreatic adenocarcinoma remains one of the most aggressive and difficult-to-treat solid tumor malignancies, with a high mortality-to-incidence ratio. Globally, pancreatic cancer ranks 12th in terms of incidence but sixth for mortality signifying its aggressive behavior and limited treatment options. While the mortality rates for many other solid tumors have substantially improved over the past few decades, temporal trends in pancreatic cancer mortality rates are quite sobering. In the United States, from 2000 to 2020, the mortality rates from pancreatic cancer have increased, whereas at the same time, mortality rates from other cancers, such as lung, colorectal, or kidney, have fallen appreciably. Is this for lack of treatment innovation? How do we improve survival for patients with pancreatic cancer? In this chapter, we discuss the recent advances and future directions with targeted therapies and immunotherapies in the treatment of pancreatic cancer, and provide the reasons for both optimism and caution for the future of systemic treatment of pancreatic cancer.