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

The field of rare cancer research is rapidly transforming, marked by significant progress in clinical trials and treatment strategies. Rare cancers, as defined by the National Cancer Institute, occur in fewer than 150 cases per million people each year, yet they collectively represent a significant portion of all cancer diagnoses. Because of their infrequency, these cancers pose distinct challenges for clinical trials, including limited patient populations, geographical dispersion, and a general lack of awareness of treatment options. Economic limitations further complicate drug development, making initiatives such as the Orphan Drug Act essential for incentivizing research. The advent of next-generation sequencing (NGS) and precision medicine has been instrumental in identifying actionable genetic alterations in parallel with an explosion in the development of genomically targeted therapies, immunotherapies, and antibody drug conjugates. Advances in clinical NGS, precision medicine, and tumor-agnostic therapies have become central to the progress in rare cancer research. The development and approval of tumor-agnostic drugs, such as BRAF, NTRK, and RET inhibitors, and immunotherapy for mismatch repair deficient/microsatellite instability-high status cancers highlight the potential of personalized treatments across diverse cancer types and across the age spectrum. Collaborative trials from cooperative groups including SWOG DART, ASCO TAPUR, NCI-MATCH, pediatric COG-match, DRUP, IMPRESS, and innovative registrational basket and platform trials (eg, VE-Basket, ROAR, LIBRETTO-001, ARROW), along with patient advocacy group-run trials like TRACK, are enhancing access to clinical trials. In addition, artificial intelligence has the potential to improve the trial matching process. An integrated approach, combining these innovations in collaboration with multiple stakeholders, is crucial for advancing rare cancer research, offering hope for better patient outcomes and quality of life.

Over the past 35 years, interferons have been explored in various formulations for the management of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), such as essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis, and remain a key tool in caring for patients with these diseases. These agents are excellent cytoreductive agents with high rates of hematologic response, are helpful in symptom management, and have a long track record of safety and manageable toxicities. More recently, they have shown promise in sustaining responses over many years, with associated reductions in driver mutations (JAK2, MPL, CALR) of these diseases, particularly in PV and ET. Since reductions in molecular mutant allele burden have been correlated with several response outcomes such as reductions in both thrombotic risk and disease progression, there is emerging proof that interferons may offer disease-modifying activity. These long-term benefits and their use as the preferred agent in young pregnant women who need cytoreduction make interferons often the first choice in young adult population who harbor a lifetime risk of progression. Looking forward, the prospect of sustained treatment-free responses, like chronic myeloid leukemia after deep molecular response, and normal life expectancy may also be on the frontier. Despite relative rookies such as JAK inhibitors in the MPN landscape, the veteran in the game, interferon, remains a key player.

CDK 4/6 inhibitors (CDK4/6i) remain part of the standard first-line treatment for patients with hormone receptor-positive metastatic breast cancer, offering demonstrable improvements in both progression-free survival and overall survival. However, resistance inevitably develops, and the optimal treatment sequencing after CDK4/6i progression remains undefined. Tumor heterogeneity and diverse resistance mechanisms-including alterations in ESR1 and PIK3CA-complicate treatment decisions in the post-CDK4/6i setting. Genomic profiling has helped to characterize these and other clinically relevant alterations, uncovering new avenues for therapeutic intervention. Building on these insights, a growing number of novel endocrine agents, phosphoinositide-3-kinase/AKT pathway-targeted therapies, and antibody-drug conjugates (ADCs) have demonstrated efficacy in biomarker-selected populations and are reshaping the treatment landscape beyond CDK4/6i progression. This chapter reviews current standards of care, emerging therapeutic options, and evolving combination strategies across biomarker-defined subgroups. We also highlight how ongoing clinical trials and advances in molecular profiling are informing personalized approaches to overcome endocrine resistance and improve patient outcomes.

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.

Chemoprevention has emerged as a promising strategy to reduce cancer incidence by using pharmacologic agents that interrupt the carcinogenesis process. This review discusses emerging insights and recent advancements in chemoprevention, emphasizing novel approaches in several cancer types. Specifically, we examine breast cancer prevention, focusing on optimized endocrine therapy dosing to enhance adherence and minimize adverse effects while maintaining efficacy. Additionally, the potential of glucagon-like peptide-1 receptor agonists to mitigate obesity-related cancer risks is evaluated, highlighting their role in addressing an increasingly prevalent risk factor in the general population. The review further explores strategies targeting colorectal cancer (CRC), specifically in familial adenomatous polyposis, a hereditary CRC syndrome that exemplifies the complex interplay between chemoprevention, genetic risk, and patient management. In prostate cancer, we highlight the evidence supporting the use of 5-alpha reductase inhibitors, detailing their effectiveness in reducing cancer incidence as well as their safety profile. Across these areas, this review underscores the importance of precision medicine, advocating for personalized approaches that balance efficacy, safety, and quality-of-life considerations. Ultimately, advancing chemopreventive strategies through targeted research and clinical trials is essential for reducing cancer burden and improving patient outcomes.

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.

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.

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.

Perioperative therapy has become a critical component in the management of resectable non-small cell lung cancer (NSCLC), particularly in the era of precision medicine. Although molecular testing is standard in metastatic NSCLC, its incorporation into early-stage disease remains essential for guiding treatment decisions. Reflex molecular testing pathways are necessary to optimize tissue utilization and ensure timely results. However, liquid biopsies, although valuable in advanced disease, have limited sensitivity in early-stage NSCLC, reinforcing the need for tissue-based next-generation sequencing. Targeted therapies have revolutionized treatment for oncogene-driven NSCLC, with adjuvant osimertinib now standard for EGFR-mutant disease and ongoing investigations into ALK tyrosine kinase inhibitors (TKIs). However, unanswered questions remain regarding the inclusion of perioperative TKI therapy, the role of molecular residual disease assessment, and whether specific TKIs offer greater benefit for high-risk subgroups. The role of immunotherapy (IO) in oncogene-driven NSCLC remains controversial. Although perioperative chemo-IO has demonstrated survival benefits in unselected NSCLC, its efficacy in EGFR, ALK, and other actionable alterations is unclear. Tumors harboring KRAS and BRAF mutations may respond better because of a more immune-inflamed microenvironment, and remains an active area of investigation. As the landscape of perioperative therapy continues to evolve, ongoing trials will help define the optimal integration of targeted therapies and IO in oncogene-driven NSCLC. Addressing these unanswered questions will be crucial in refining treatment strategies and improving patient outcomes.