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

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the importance of implementing ATB stewardship recommendations in routine oncology practice. Microbiota-centered interventions are now being explored to treat gut dysbiosis and optimize ICI responses. Early-phase clinical trials evaluating fecal microbiota transplantation (FMT) from ICI responders or healthy donors have shown that this approach is safe and provided preliminary data on potential efficacy to overcome both primary and secondary resistance to ICI in melanoma, non-small cell lung cancer, and renal cell carcinoma. More targeted interventions including live bacterial products including Clostridium butyricum and Akkermansia massiliensis represent novel microbiome-based adjunct therapies. Likewise, dietary interventions, such as high-fiber diets, have shown promise in enhancing ICI activity. In this ASCO Educational Book, we summarize the current state-of-the-evidence of the clinical relevance of the intestinal microbiota in cancer immunotherapy and provide a practical guide for ATB stewardship.

Lung cancer is one of the leading causes of cancer-related mortality worldwide, with most cases diagnosed at advanced stages where curative treatment options are limited. Low-dose computed tomography (LDCT) for lung cancer screening (LCS) of individuals selected based on age and smoking history has shown a significant reduction in lung cancer-specific mortality. The number needed to screen to prevent one death from lung cancer is lower than that for breast cancer, cervical cancer, and colorectal cancer. Despite the substantial impact on reducing lung cancer-related mortality and proof that LCS with LDCT is effective, uptake of LCS has been low and LCS eligibility criteria remain imperfect. While LCS programs have historically faced patient recruitment challenges, research suggests that there are novel opportunities to both identify and improve screening for at-risk populations. In this review, we discuss the global obstacles to implementing LCS programs and strategies to overcome barriers in resource-limited settings. We explore successful approaches to promote LCS through robust engagement with community partners. Finally, we examine opportunities to enhance LCS in at-risk populations not captured by current eligibility criteria, including never smokers and individuals with a family history of lung cancer, with a focus on early detection through novel artificial intelligence technologies.

Financial toxicity, or the financial burden patients experience because of medical costs, can lead to negative patient effects including lower quality of life, compromised clinical care, and worse health outcomes. People with cancer and survivors are more likely to have financial toxicity than those without cancer, and patients with breast cancer are uniquely at risk. Patients with breast cancer often require multimodal treatment (surgery, radiation, and/or systemic therapy) and adjuvant hormonal therapy can continue for years after primary treatment. With improved disease outcomes, patients with breast cancer have prolonged survivorship often lasting decades but may carry chronic toxicities from treatment; both ongoing treatment of metastatic disease and long-term surveillance include continued tests, imaging, and medical visits that add to the cumulative burden on patients and their families. Additionally, breast cancer predominately affects women, who are more likely to have dual caregiver responsibilities, and increasingly is diagnosed in younger patients, who may have fertility preservation expenses and are more likely to experience education and/or employment disruption. When faced with high costs, patients may face difficult decisions regarding what sacrifices they are willing to endure to receive care. Interventions designed to reduce financial toxicity are moving out of the pilot phase, and ongoing randomized trials are expected to provide evidence into the effectiveness of financial navigation programs. Further work to address financial toxicity in breast cancer at the patient-provider, institutional, and governmental levels is needed for comprehensively better financial outcomes and quality of life.

Immune checkpoint inhibitors are cancer therapeutics that have shown remarkable success in extending lives in many cancers, including melanoma, MSI-high cancers, and other cancers. However, these therapeutics have not shown benefit for many patients with cancer, especially those with advanced cancer diagnoses. In addition, many patients develop resistance to these therapeutics and/or life-altering adverse events that can include cardiotoxicity, pneumonitis, thyroiditis, pancreatitis, and hepatitis. Extensive efforts to improve cancer care by uncovering mechanisms of resistance to immune therapy in solid tumors have led to identification of new sources of resistance and to the development of new approaches to activate or sustain antitumor immunity. Chronic stimulation of T cells by tumors and by checkpoint inhibitors can lead to a progressive state of T-cell exhaustion. Chronic T-cell activation by the tumor microenvironment (TME) or immune therapeutics can upregulate the expression and function of alternate checkpoints, including the T-cell protein LAG-3. Persistent interferon signaling in the TME can drive epigenetic changes in cancer cells that enable tumors to counter immune activation and disrupt tumor cell elimination. In addition, immune-suppressive macrophages can flood tumors in response to signals from dying tumor cells, further preventing effective immune responses. New clinical developments and/or approvals for therapies that target alternate immune checkpoints, such as the T-cell checkpoint LAG-3; myeloid cell proteins, such as the kinase phosphoinositide 3-kinase gamma isoform; and chronic interferon signaling, such as Jak 1 inhibitors, have been approved for cancer care or shown promise in recent clinical trials.

Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer, where the endemic subtype is strongly associated with Epstein-Barr virus (EBV) infection, whereas emerging data suggest that a subset of nonendemic NPC may be associated with human papillomavirus (HPV) infection. Nonetheless, treatment advances have been driven by clinical trials conducted in endemic NPC, investigating optimal sequencing of chemotherapy and immune checkpoint inhibitors with radiotherapy for locoregionally advanced disease. The preference for induction chemotherapy (IC) in these patients has also led to evolution in the concept of radiotherapy target delineation. Because of its association with EBV, plasma EBV DNA is an archetypal biomarker for endemic NPC, and it is being explored for precise stratification and treatment individualization in several ongoing trials. In the space of recurrent or metastatic-NPC, with the advent of platinum-doublet chemotherapy and anti-PD-1 antibody as the new standard of care, several trials are investigating new immunotherapeutic combinations, bispecific antibodies, and antibody-drug conjugates that have demonstrated promise in early phase trials. An important advance for NPC in 2025 is the update of the 9th version of the TNM staging system, which has introduced several key changes, including downgrading of the TNM stage groupings for localized disease, and splitting of metastatic NPC into IVA and IVB based on the number of metastatic lesions. These revisions would have implications for the treatment and design of future trials. These advances are also relevant to nonendemic NPC, where evidence is inconclusive whether this disease responds differently to current treatments compared with endemic NPC.

Locally advanced non-small cell lung cancer (NSCLC) is primarily treated with multimodality therapy, which has undergone significant advancements over the years. Recently, the management of resectable NSCLC has evolved to provide patients more effective and tolerable options to prevent disease recurrence and increase rates of cure. In addition to surgical and screening advances, the use of tailored neoadjuvant, perioperative, and adjuvant therapies after resection has played a pivotal role. Innovations in surgical techniques and perioperative care, with a focus on precision medicine, have expanded the eligibility of patients for curative surgery. These advancements have been shown to improve patient outcomes by reducing both morbidity and mortality. This manuscript outlines the developments in the treatment of locally advanced NSCLC.

The art of sequencing therapy in the management of breast cancer is a multifaceted challenge that demands the careful integration of clinical trial data, real-world evidence, and individualized patient factors to guide treatment decisions. As the therapeutic landscape evolves rapidly with new agents and combinations, clinicians are confronted with critical decisions on how best to order treatments to maximize benefit, minimize toxicity, and preserve future options. For patients with estrogen receptor-positive (ER+) disease, this review discusses how emerging resistance patterns after cyclin-dependent kinase 4 and 6 inhibitors require careful re-evaluation of subsequent endocrine and targeted therapies, as well as chemotherapy, emphasizing the need for evidence-based strategies and ethical crossover designs in clinical trials. In addition, for both ER+ and ER- metastatic breast cancer (MBC) with nonoverexpressed human epidermal growth factor receptor 2 (HER2), this review highlights pivotal trials investigating antibody-drug conjugates (ADCs)-including trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan-and the challenges related to control arm selection and crossover that may affect outcome interpretation. Finally, for patients with HER2-positive disease, the review explores first-line and maintenance strategies-including insights from landmark trials like CLEOPATRA and PATINA-and addresses the impact of brain metastases on sequencing decisions. By critically appraising current data and identifying gaps in biomarker-guided and sequencing-specific strategies, this review provides practical insights to inform clinical practice and optimize personalized treatment plans for patients with MBC.

Antibody-drug conjugates (ADCs), bispecific antibodies that engage T cells (BsAbs), and chimeric antigen receptor (CAR) T cells are widely used standard-of-care therapies that have revolutionized the treatment of lymphoid and plasma cell malignancies. With recent regulatory approvals, these therapies are poised to also revolutionize the treatment of common solid tumors and become a part of the everyday lexicon, the ABCs, of the practicing oncologist. Drawing from experience in hematology, we review the early, late, and rare toxicities of ADCs, BsAbs, and CAR T cells and provide general principles for their management.

Chronic lymphocytic leukemia (CLL) remains an incurable disease, except in rare cases treated with allogeneic stem-cell transplantation or favorable-risk CLL treated with chemoimmunotherapy. Treatment initiation follows the Rai and Binet staging systems, but the International Workshop on Chronic Lymphocytic Leukemia criteria emphasize active disease rather than stage alone. Early treatment in asymptomatic, high-risk patients has not shown an overall survival benefit, even with targeted therapies such as Bruton's tyrosine kinase and BCL2 inhibitors. The watch-and-wait strategy remains standard, although future trials may refine early treatment indications for specific high-risk groups.