Current Opinion in Oncology最新文献

Purpose of review: Despite recent advances in immunotherapy treatment for metastatic, early-stage nonsmall cell lung cancer (NSCLC), palliative, adjuvant, neoadjuvant, and perioperative treatment options, further development is needed. Exploring new frontiers of immuno-oncology is necessary. Researchers are interested in a therapeutic vaccination model.

Recent findings: In this paper, we provide a review of the latest lung cancer therapeutic vaccines.We describe strategies for antigen selection and delivery platforms. As of 5th of August 2024, we have reviewed ongoing clinical trials and results.We summarize most of the important clinical trials of novel vaccines, the way of action, and available clinical data. We also discuss the pros and cons of various types of therapeutic vaccines.

Summary: Until recently, clinical trial results were mixed regarding the efficacy of therapeutic vaccines in lung cancer.Developing next-generation sequencing and bioinformatic technologies has helped identify suitable antigens. New personalized vaccines are based on neoantigens specific to unique tumor mutations.Neoantigens, instead of tumor-associated antigens, better delivery systems and adjuvants will improve antigen presentation and immune system activation.Combining these therapeutic vaccines with other therapeutic approaches will improve and prolong the response.

Purpose of review: Recent years have witnessed significant advancements in the treatment of lung cancer with immunotherapy, primarily centered on immune checkpoint inhibitors (ICIs). Numerous clinical studies have evaluated or are currently evaluating the clinical benefits of neoadjuvant, adjuvant, and perioperative use of ICIs. These findings have notably reshaped the landscape of perioperative treatment for nonsmall cell lung carcinoma (NSCLC).

Recent findings: Comparing different treatment modes, adding ICIs in the adjuvant phase to neoadjuvant treatment with ICIs and chemotherapy may not improve survival outcomes for patients with resectable NSCLC and may be associated with increased adverse events. For prognostic factors, ctDNA minimal residual disease (MRD) status might serve as an early predictor of achieving pathological remission. For study endpoints, a positive result with PFS as the primary endpoint may not necessarily translate into overall survival benefits.

Summary: For perioperative immunotherapy, challenges persist, including the current lack of sensitive and reliable biomarkers, the effect of neoadjuvant therapy on surgical risk as well as the selection of the appropriate study endpoint. In this review, we discuss recent and ongoing trials investigating strategies of neoadjuvant, adjuvant and perioperative immunotherapy in NSCLC, while also proposing considerations for future directions in this continuously evolving field.

Purpose of review: Thymic epithelial tumors (TETs) are a diverse group of malignancies that include thymomas (T), thymic carcinomas (TC), and thymic neuroendocrine tumors. Given the rarity of this disease, evidence defining the optimal treatment approach in the advanced/metastatic setting is limited. This article reviews the latest advances in systemic therapy for TETs, with a special focus on immunotherapy and targeted therapy strategies.

Recent findings: Multiple recent efforts have been made to integrate novel immunotherapies and targeted therapy approaches into the current treatment algorithm for T and TC. In addition to trials of checkpoint inhibitor monotherapy, combinatorial approaches with novel immunotherapies or targeted therapies are being explored. Molecular profiling may help identify druggable targets, further optimizing outcomes in this population.

Summary: Immune checkpoint inhibitor therapy has shown promising activity in TETs patients. However, toxicity in an unselected cohort, particularly in T patients, can be substantial, and therefore it is not recommended outside of clinical trials. Until additional research validates biomarkers to safely select patients for immunotherapy, targeted therapies remain a reasonable second-line option. Contemporary next-generation sequencing panels may be applied to identify druggable targets in the absence of standard treatment.

Purpose of review: Growth and survival of hormone receptor positive breast cancer cells are dependent on circulating hormones (e.g., estrogen and progesterone). Endocrine therapy improved outcomes in both early and advanced hormone receptor positive breast cancer. These treatments include drugs with different mechanisms of action, namely selective estrogen receptor modulators (SERM), aromatase inhibitors, and selective estrogen receptor degraders (SERDs). SERDs represent estrogen receptor antagonists, favoring its degradation and thus interfering with proliferation genes transcription and activation. Fulvestrant is the first approved SERD, administered intramuscularly for treating advanced breast cancer.

Recent findings: Oral SERDs have been tested to overcome the limitation of the intramuscular administration, and to increase SERD bioavailability. Recently, an oral SERD, Elacestrant, has been approved by the Food and Drug Administration (FDA) for patients carrying an ESR1 mutation. In fact, oral SERDs seem to be effective in tumors harboring ESR1 mutations, a well known mechanism of resistance to endocrine therapy (especially aromatase inhibitors).

Summary: More recently, oral SERDs have been tested in patients with early hormone receptor positive breast cancer, although their impact on survival and in this curative setting compared to standard endocrine therapy still needs to be elucidated. The best timing and duration of SERD administration and specific biomarkers in (neo)adjuvant setting remain largely unknown.

Purpose of review: Health disparities or inequities, which are defined as differences in the quality of medical and healthcare between populations among racial, ethnic, and socioeconomic groups, have been validated in numerous studies as determinants of survival and quality of life in different diseases, including cancer.Compared to the improvement in overall survival in developed countries in relation to better diagnostic opportunity and novel therapeutic approaches, low and middle-income countries still have significant barriers in accessing these therapies.The potential impact of overcoming these barriers is immense and offers hope for better outcomes.

Recent findings: There is great heterogeneity in the diagnostic and therapeutic approach to multiple myeloma among different latitudes. Latin America has been characterized by important limitations in using the best technologies currently available in developed countries.

Summary: Overcoming health disparities in multiple myeloma in LMICs could help improve survival and quality of life outcomes. Likewise, it is necessary to increase the representation of the Latin population in clinical studies, primarily in our region.

Purpose of review: To evaluate and summarize the current clinical efficacy, safety, treatment patterns, and potential biomarkers, to guide future treatment strategies for nonsmall cell lung cancer (NSCLC), improve patient prognosis, and provide a scientific basis for personalized therapy.

Recent findings: In recent years, the class of immune checkpoint inhibitors (ICIs), with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors at the helm, has catalyzed groundbreaking advancements within the perioperative treatment milieu for NSCLC. With the positive results of several phase III clinical trials, perioperative immunotherapy has been confirmed to significantly reduce the risk of postoperative recurrence in resectable NSCLC, becoming the new standard for perioperative treatment of stages II to III NSCLC. With the advent of the perioperative immunotherapy era, clinical issues such as the selection of the treatment population, the choice of regimen, the duration of treatment, whether patients with pCR need further adjuvant therapy, and the comprehensive management of patients throughout the perioperative period have attracted widespread attention.

Summary: The perioperative treatment of NSCLC has fully entered the era of immunotherapy. Multiple clinical studies have confirmed that perioperative immunotherapy can significantly improve the survival benefit of resectable stages II to III NSCLC, establishing a new standard for the perioperative treatment of stages II to III NSCLC.

Purpose of review: We aim to summarize the current knowledge on the management of early-stage classical Hodgkin lymphoma, with a focus on conventional strategies, incorporation of immunotherapies and exploration of novel prognostic markers.

Recent findings: Long-term data on combined modalities (associating chemotherapy and radiotherapy) still supports their benefit in terms of progression free survival compared to chemotherapy alone in both early favourable and early unfavourable interim PET-negative classical Hodgkin Lymphoma. Novel agents, such as Brentuximab Vedotin and checkpoints inhibitors show promising and impressive results when added to first-line treatment. Various strategies have been used, mainly in phase 2 non randomized clinical trials. Interim PET-scan has limited prognostic value and its role in regimens incorporating immunotherapies is yet unknown. Other prognosis markers emerge, such as metabolic tumour volume and circulating tumour DNA. By reflecting tumour burden pretreatment and minimal residual disease on treatment, they might be useful tools guiding treatment decisions.

Summary: Novel immunotherapy agents are likely to change the landscape in front-line management of classical early-stage Hodgkin lymphoma by combined modality treatment. Despite encouraging recent data, proof of their efficacy and safety on the longer term are still needed. Treatment decisions might be guided by new promising prognosis markers but their use in clinical practice is still to be determined.

Purpose of review: Antibody-drug conjugates (ADCs), consisting of monoclonal antibodies (mAbs) covalently linked to cytotoxic drugs via chemical linkers, are a kind of promising tumor immunotherapy. ADCs also face a number of challenges, including unavoidable adverse effects, drug resistance, tumor targeting and payload release. To address these issues, in addition to optimizing the individual components of ADCs, such as new payloads, linkage sites and new targets, and using bispecific antibodies to increase precision, attention should be paid to optimizing the dosage of ADCs.

Recent findings: There are currently 7 ADCs approved for marketing by the Food and Drug Administration (FDA) for hematological malignancies, and dozens of other ADCs are either in clinical trials or in the process of applying for marketing. In recent clinical studies targeting ADCs in hematologic malignancies, in addition to validating effectiveness in different indications, researchers have attempted to combine ADCs with other chemotherapeutic agents in anticipation of increased therapeutic efficacy. Furthermore, the availability of bispecific antibodies may increase the safety and efficacy of ADCs.

Summary: This review summarized the progress of research on ADCs in hematological malignancies, the challenges being faced, and possible future directions to improve the efficacy of ADCs, which can provide novel insight into the future exploration of ADCs in the treatment of hematological malignancies.

Purpose of review: Historically, salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDT/ASCT) was the mainstay approach for relapsed or refractory classic HL. The emergence of novel agents for HL, such as brentuximab vedotin and programmed death-1 (PD-1) blockade has revolutionized therapeutic strategies, yielding excellent results. This review aims to provide a comprehensive overview of new salvage therapies and offer insights into forthcoming therapeutic options.

Recent findings: The incorporation of brentuximab vedotin and PD-1 blockade into salvage therapy before HDT/ASCT has led to markedly improved outcomes. Notably, PD-1 based salvage studies yield posttransplant 2-year progression-free survival rates approaching 90%, marking a significant advancement in the treatment of Hodgkin lymphoma (HL). Studies are beginning to explore nontransplant treatment approaches following front-line treatment failure and may identify certain risk groups eligible for these strategies.

Summary: The landscape of HL treatment is rapidly evolving, leading to significant changes in the standard of care. Novel agents are now administered earlier in the disease course, resulting in higher cure rates. The focus of treatment is shifting towards achieving cure with minimal toxicity, reducing exposure to various agents, and advancing research in optimizing treatment sequencing and patient selection for less intensive therapies.