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

Treatment of multiple myeloma (MM) has evolved significantly over the past few decades. Up-front treatment options expanded from doublet regimens to triplets and now to quadruplets. Monoclonal antibodies have significantly contributed to this paradigm shift. Their incorporation into frontline regimens demonstrated improved survival outcomes irrespective of transplantation eligibility. Autologous hematopoietic stem-cell transplant (ASCT) remains standard in frontline consolidation therapy with recent expansion of eligibility, including older adults and patients with renal failure. The growing understanding of physiologic age and frailty, as well as improvements in supportive care, has made this possible. Bispecific T-cell engager (BiTE) antibodies are heralding a new age of treatment of MM with high response rates in patients with relapsed or refractory MM. With the impressive responses seen, these treatments are being studied in earlier lines of therapy and in combination with other therapies. With this rapidly evolving field of immunotherapy in MM, the goal of this review was to discuss the latest advances in MM treatment, focusing on up-front quadruplet therapy, the role of ASCT in the modern era, and the evolving role of BiTEs in up-front therapy.

Therapeutic advances across the gynecologic cancer continuum have resulted in improvements in patient care and outcomes over the past decade, yet challenges remain. In ovarian cancer, the evolution of poly (ADP-ribose) polymerase (PARP) inhibitor therapy has resulted in marked benefit for patients with BRCA-mutated cancers but has also unmasked the need for new therapies in patients whose cancers are proficient in homologous recombination and lack vulnerability to PARP inhibitors, as well as for those patients whose cancers progress on PARP inhibitors. In endometrial cancer, immune checkpoint inhibitors (ICIs) have improved outcomes for patients receiving first-line therapy for advanced or recurrent disease when combined with standard-of-care chemotherapy. However, there remains uncertainty around which patients are most likely to benefit from the addition of immunotherapy, and treatment beyond first-line therapy remains an area of high unmet need. Similarly, ICIs added to chemotherapy for recurrent or metastatic cervical cancer or to chemoradiation for high-risk locally advanced cervical cancers has resulted in improved outcomes, but treatment options beyond this remain limited. Across gynecologic cancers, antibody-drug conjugates (ADCs) hold the promise for further improvement in patient outcomes. A prime example is the demonstrated benefit of mirvetuximab soravtansine over other standard chemotherapy options in folate receptor alpha-high platinum-resistant ovarian cancer. Maximizing such potential will require developing a deeper understanding of relationships between ADC target expression and activity, mechanisms of resistance, and potential approaches to sequencing. Beyond ADCs, additional therapies, including those targeting DNA damage response, remain in development.

Every year, many children around the world are diagnosed with cancer. While the overall survival of pediatric patients with cancer is high and constantly improving with clinical trials and adjustments to existing treatment protocols, many of these patients experience infectious complications that contribute to morbidity and mortality. As infectious complications pose a serious risk for these patients, it is imperative to generate and incorporate evidence-based tools into standards of care to provide optimal supportive care. Examples of evidence-based tools that improve medical care include risk prediction models and clinical practice guidelines. This article describes the process used to generate and implement these important supportive care tools, providing examples of their use in high-resource medical settings. Additionally, this article further explores barriers to their use especially in low- and middle-income countries, providing examples of how to adjust for local resource availability. By focusing on cost-effective and sustainable approaches, these tools can be used by health systems worldwide to reduce morbidity and mortality among pediatric oncology patients.

The therapeutic landscape of small cell lung cancer (SCLC) is undergoing a paradigm shift with the emergence of delta-like ligand-3 (DLL3)-directed therapies, particularly tarlatamab, a first-in-class bispecific T-cell engager designed to bind to cluster of differentiation-3 on T cells and DLL3 on tumors cells, demonstrating promising efficacy, including potential intracranial activity, and a manageable safety profile. By leveraging biologic insights into SCLC subtypes and DLL3 expression, these therapies mark a step forward in precision immunotherapy for this recalcitrant disease. As new DLL3-targeting agents continue to evolve through bispecific, trispecific constructs, antibody-drug conjugates, and chimeric antigen receptor-based approaches, they bring hope for improved outcomes in SCLC and other high-grade neuroendocrine carcinomas. Importantly, the thoughtful incorporation of toxicity mitigation strategies, equitable access, and multidisciplinary care models will be critical to ensure that clinical advances translate into meaningful, real-world benefits. The challenge ahead lies in balancing efficacy with patient quality of life, financial burden, and time toxicity, an effort that requires continuous innovation, collaboration, and a patient-centered approach.

The rising incidence of early-onset colorectal cancer (EOCRC) presents a growing challenge to traditional approaches in screening, treatment, and survivorship. EOCRC is increasingly recognized as a biologically distinct entity, driven by complex inter-related biological, genetic, behavioral, and socioenvironmental factors. This chapter reviews the molecular and clinical features that distinguish EOCRC, with attention to emerging precision oncology strategies, including germline testing, tumor genomic profiling, and biomarker-directed therapies. In metastatic disease, recent advances in targeting BRAF V600E, KRAS G12C, HER2 amplification, and microsatellite instability-high (MSI-H)/mismatch repair deficiency tumors have reshaped therapeutic paradigms. Tumor sidedness and metastatic site patterns are now recognized as predictive and prognostic factors. In localized disease, neoadjuvant immunotherapy for MSI-H tumors and nonoperative management are redefining standard care, with special relevance to younger patients seeking fertility preservation or organ-sparing approaches. The chapter also addresses key gaps in EOCRC care, including underutilization of fertility preservation counseling and limited guidance for cancer management during pregnancy. A multidisciplinary, lifecycle-based framework is essential to optimize outcomes and improve quality of life for this unique and growing patient population.

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.

Mucosal melanoma (MM) is a rare and aggressive subtype of melanoma arising from mucosal tissues, with distinct genomic and clinical characteristics compared with cutaneous melanoma (CM). Despite therapeutic advancements, MM remains challenging to treat because of late diagnosis, high heterogeneity, and limited efficacy of conventional therapies. This review synthesizes current knowledge on the genomic landscape of MM and explores the tumor microenvironment that influences treatment resistance. Emerging therapeutic approaches, including neoadjuvant and adjuvant therapies, are critically evaluated. Targeted therapy (eg, BRAF/MEK and KIT inhibitors) demonstrated comparable efficacy in advanced MM and CM. Although immune checkpoint inhibitors show promise in CM, their efficacy in MM is modest, with antiangiogenic-based combination therapies offering potential improvements. Preclinical and ongoing clinical trials underscore the need for personalized treatment strategies on the basis of molecular profiling. This review emphasizes the urgency for further research to address the unmet needs in MM management and improve patient outcomes.

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.