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

Despite being a cornerstone of cancer treatment advancement, clinical trials remain inaccessible for many patients because of structural, socioeconomic, and systemic barriers. In this multidisciplinary perspective piece, stakeholders from patient advocacy, community oncology, industry, and academic medicine offer a collaborative overview of key challenges and practical solutions to improve trial accessibility. Patient advocates highlight the need to address language barriers, financial toxicity, and underrepresentation through community engagement and patient-centered trial design. Community oncologists underscore infrastructure limitations, generalist practice burdens, and misaligned trial offerings, calling for eligibility reform and cooperative trial models. Industry partners examine how overly restrictive criteria and inconsistent protocol practices hinder diversity and propose portfolio-wide strategies, such as protocol watch lists, for inclusive design. Academic oncologists focus on trial complexity, investigator burden, and limited generalizability, advocating for pragmatic and decentralized trial paradigms. Together, these perspectives underscore the shared responsibility across sectors to modernize clinical trial design, reduce access barriers, and ensure that trial participation becomes a standard and equitable component of cancer care.

Although innovation in cancer treatment has improved cure rates and survival, the costs have escalated beyond societies' ability to pay. Cancer care costs in the United States are expected to rise to 245 billion by 2030. In this health policy session, we focused on three cost-containment strategies, and their potential impact on cancer care delivery. Site Neutrality: Curbing the Cost of Cancer Care, but at What Risk?, explores legislation that would introduce payment parity across differing sites of care: elimination of facility fees in hospital owned practices and shift of billing for oncology infusions away from hospital owned practices. Unintended consequences could reduce access to care for vulnerable populations, shift costs to patients, and reduce safety. Post-Pandemic Digital Health Reimbursement: Impact on Access to Care, explores how the emergency waivers, licensure flexibilities, and parity reimbursement necessitated by COVID-19 shepherded innovation that outpaced the regulatory framework needed for long-term sustainability. Today, telehealth services, hospital at home, remote patient monitoring, and decentralized clinical trial enrollment face reintroduction of regulatory and payment barriers. Will we live to see efficacy-based pricing for cancer drugs? Learning from international models, explores how lack of drug price negotiation has led to higher prices in the United States compared with Canada and Europe. Comparative clinical effectiveness pricing systems compare the value of each drug to standard treatments. Comparative cost-effectiveness programs look at the incremental cost per additional unit of health gained above the standard of care. The United States could learn from these approaches used in comparable countries.

The discovery of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and the subsequent development of targeted therapeutics represents a groundbreaking advancement in care, shifting the treatment paradigm to more personalized approaches with significantly improved survival because of our evolving understanding of the pathobiology and molecular underpinnings of the disease. First-line regimens for patients with EGFR-positive NSCLC now include EGFR tyrosine kinase inhibitor monotherapy or combination therapy with osimertinib and chemotherapy or amivantamab and lazertinib. There are several pros and cons to each approach of monotherapy vs combination therapy such that we must carefully weigh the balance between efficacy, toxicity, quality of life, and subsequent treatment options with our patients to determine the best approach at diagnosis of advanced disease. Importantly, there are subpopulations of patients who may benefit more from combination therapy, including those with TP53 comutations, high tumor burden, brain metastases, and/or detectable ctDNA. This review discusses current data and treatment approaches for the management of advanced/metastatic EGFR-mutant NSCLC, with a particular emphasis on the complexity of first-line management.

Thirty-two million Americans live in rural counties and have no access to multidisciplinary cancer care, and patients with cancer describe a greater number of unfavorable social determinants of health (SDoH), experience more serious financial hardship as well as greater symptom burden, and are more likely to die of cancer. Delivering effective symptom management may be achieved through adoption of a hub and spoke model, which connects rural community care sites with a cancer center. Modern technologies (electronic medical record and virtual telehealth), advanced practice provider care models, and engagement in symptom management clinical trials can extend more optimal care to connected rural sites. Pragmatic examples of addressing these care barriers include systematic and proactive assessment of SDoH, supported by navigation and social services, and telehealth-enabled palliative care (PC). In low- and middle-income countries, access to supportive cancer care services is very limited, especially in rural areas. Digital health interventions, primarily limited to apps, and community health workers (trained volunteer care providers) have successfully enabled vital symptom management services. Access to PC, considered a basic human right, is unfortunately not available in many parts of the world, especially in rural areas of not only low- and middle-income but also high-income countries. Multiple approaches to deliver effective symptom management have been described but need to be tailored to the respective local health care infrastructure, resources, culture, and social, economic, and political environment.

Blinatumomab has rapidly emerged as a cornerstone in the treatment of B-cell ALL (B-ALL) across age and risk groups. Initially approved for minimal residual disease (MRD)-positive adult B-ALL in 2018, its indications have since expanded after pivotal trials demonstrating significant efficacy. The BLAST and E1910 trials highlighted the benefit of blinatumomab in adults in MRD-positive and MRD-negative remission, respectively, with notable improvements in overall survival and relapse-free survival. In pediatric populations, studies such as the AALL1731 and a landmark trial in infants with KMT2A-rearranged B-ALL demonstrated striking reductions in relapse when blinatumomab was added to standard regimens. Similarly, in Philadelphia chromosome-positive B-ALL, blinatumomab-based regimens have enabled chemotherapy minimization while achieving durable remissions. Despite these advances, the rapid integration of blinatumomab into standard care poses challenges related to administration, toxicity management, and equitable access. Variability in inpatient observation durations, infusion bag sizes, home health availability, and handling of infusion-related complications underscore the need for standardized delivery models. Additionally, low-grade and long-term toxicities-such as neurotoxicity, cytokine release syndrome, and hypogammaglobulinemia-remain undercharacterized. Looking forward, research is focusing on optimizing the use of blinatumomab, including its integration into reduced-intensity or chemotherapy-free regimens, alternative dosing schedules, and subcutaneous administration. As clinical use expands, emphasis must shift toward developing equitable, patient-centered delivery strategies and understanding the full spectrum of toxicities to ensure optimal and accessible care for all patients with B-ALL.

Novel approaches in molecular imaging and targeted therapeutics are transforming the management of renal cell carcinoma (RCC) and urothelial carcinoma (UC). This review focuses on three key areas of innovation: molecular imaging, hypoxia-inducible factor-2α (HIF-2α) inhibition, and antibody-drug conjugates (ADCs). In molecular imaging, prostate-specific membrane antigen positron emission tomography/computed tomography has shown promise in RCC, while novel tracers targeting carbonic anhydrase IX and nectin-4 are emerging for RCC and UC, respectively. These approaches may enable better characterization of disease and treatment response monitoring. HIF-2α inhibition represents a breakthrough in targeting the fundamental pathobiology of clear cell RCC, with belzutifan demonstrating significant clinical benefit in both von Hippel-Lindau disease and sporadic RCC. Next-generation HIF-2α inhibitors, including casdatifan, show promising early clinical results with distinct pharmacologic properties. ADCs have become a cornerstone of UC treatment, with enfortumab vedotin plus pembrolizumab now approved as first-line therapy. Multiple human epidermal growth factor receptor 2 (HER2)-directed ADCs have shown efficacy in HER2-expressing UC, including trastuzumab deruxtecan, which recently received tumor-agnostic approval. While ADC development in RCC faces unique challenges, novel approaches including immunostimulatory payloads and bispecific antibodies are being explored. The integration of these advances in molecular imaging and therapeutics offers opportunities for more personalized treatment approaches in RCC and UC.

Liquid biopsy encompasses a variety of molecular approaches to detect circulating tumor DNA (ctDNA) and has become a powerful tool in the diagnosis and treatment of solid tumors. Current applications include comprehensive genomic profiling for identifying targetable mutations and therapeutic resistance mechanisms, with emerging applications in minimal residual disease detection and treatment response monitoring. Increasingly, the potential for liquid biopsy in guiding treatment decisions is under active investigation through prospective clinical trials using ctDNA-adaptive interventions in patients with early-stage and metastatic cancers. Limitations arise on the basis of the sensitivity and feasibility of individual liquid biopsy assays; nonetheless, emerging technologies set the stage for improving these shortcomings. As the global oncology community continues to ascertain the clinical value of liquid biopsy across the continuum of patient care, this minimally invasive approach heralds a significant advancement in the promise of precision oncology.

Older patients with ALL often have high-risk disease characterized by adverse-risk cytogenetic and molecular abnormalities, as well as Philadelphia chromosome (Ph)-positive and Ph-like phenotypes. They often have comorbidities resulting in poor tolerance to chemotherapy and are at risk of developing therapy-related myeloid neoplasms (t-MNs). In Ph-negative ALL, the duration and intensity of chemotherapy was reduced, and outcomes improved with the addition of inotuzumab ozogamicin (InO) and blinatumomab into the frontline setting. However, t-MNs are still being observed, prompting the development of chemotherapy-free regimens with InO and blinatumomab as well as chimeric antigen receptor (CAR) T-cell therapies in high-risk disease. In Ph-positive ALL, chemotherapy and allogeneic hematopoietic stem-cell transplantation (HSCT) were historically considered a standard of care. However, the introduction of blinatumomab and newer-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) into the frontline setting significantly improved outcomes. The combination of blinatumomab and ponatinib induced high rates of complete molecular responses and excellent survival, without reliance on HSCT. A subset of patients with elevated WBC count at diagnosis are at particular risk of CNS and systemic relapse and may require additional strategies such as incorporating one to two cycles of high-dose methotrexate/cytarabine into consolidation, and potentially CAR T cells. In T-cell ALL, adding venetoclax into the frontline setting has improved outcomes. In early T-cell precursor ALL, HSCT is still needed. To further improve outcomes in older patients, novel agents such as subcutaneous blinatumomab, CAR T cells, newer-generation TKIs, and menin inhibitors should be investigated in the frontline setting.

Recent advances in defining low- and intermediate-risk myelodysplastic syndromes (MDSs) have emphasized the critical role of molecular characterization using next-generation sequencing (NGS). Molecular profiling significantly enhances diagnostic precision, classification, and risk stratification, thereby informing therapeutic decisions, including the timing of hematopoietic stem-cell transplantation (HSCT). The Molecular International Prognostic Scoring System integrates clinical and molecular data, reclassifying and upstaging a substantial number of patients compared with previous prognostic systems, possibly allowing for more tailored therapeutic interventions. The novel therapeutic agents luspatercept and imetelstat have been particularly impactful. Luspatercept, which is effective in lower-risk (LR)-MDS, especially but not only in SF3B1-mutated cases, promotes late-stage erythroid maturation and transfusion independence (TI). Imetelstat, a telomerase inhibitor, induces TI while demonstrating disease-modifying effects as it significantly reduces mutation allele frequencies in patients who respond. These agents exemplify personalized medicine, emphasizing treatment selection and timing based on individual molecular and clinical features. Current research focuses on optimizing therapeutic strategies and exploring combination treatments to improve clinical outcomes.