Expert Opinion on Biological Therapy最新文献

Introduction: Gastric adenocarcinoma (GAC) remains a prevalent cancer worldwide and its incidence is increasing in South America. The heterogenous nature of GAC makes advances in management challenging.

Areas covered: Despite challenges, recent therapeutic targets are individualizing treatment. For localized disease with microsatellite-instability-high/deficient mismatch repair, immunotherapy is now an adopted practice. In the advanced unresectable setting, those harboring human epidermal growth factor receptor-2 (HER2) expression continue to be a separate entity.

Expert opinion: Future targets are developing. Among these include claudin 18.2 (CLDN18.2), fibroblast growth factor receptor 2b (FGFR2b), and trophoblast cell surface antigen-2 (TROP-2). FDA approval of zolbetuximab's, an anti-CLDN 18.2 monoclonal antibody, is expected soon. Additionally, bemarituzumab, ananti-FGFR2b monoclonal antibody, has shown improvements in combination with chemotherapy in those with HER2 negative GAC with FGFR2 overexpression. This combination is now being investigated in a phase 3 trial. Lastly, TROP-2 has emerged as an exciting solid tumor target and study is expected in GAC. All three of these therapeutic targets have seen an abundance of drug development in recent years, and we anticipate newer targeted agents driving therapeutic decisions in GAC in the coming years.

Introduction: Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adult patients. The landscape of CLL therapy has changed in the last decades with the introduction of antibody-based therapies and novel targeted agents resulting in improved outcomes.

Areas covered: This article describes the use of monoclonal antibodies, bispecific antibodies and antibody-drug conjugates in the treatment of relapsed and refractory CLL. The mechanism of action and clinical applications and safety of antibody-based therapies, both as monotherapy and in combination with other drugs, are discussed. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Expert opinion: Antibody-based therapeutic strategies have drastically changed the treatment of CLL, as they have introduced the concept of boosting immune responses against tumor cells. While immunotherapy is generally effective, some treatment failure can occur due to antigen loss, mutation, or down-regulation, and this remains the main obstacle to cure. The development of novel antibody therapies, including their combinations with targeted drugs and bispecific antibodies might help to reduce toxicity and improve efficacy.

Introduction: Treatment of ulcerative colitis (UC) aims to reduce symptoms and complications by decreasing intestinal inflammation. A proportion of patients do not respond to, do not tolerate, or are inappropriate candidates for current therapies. Interleukin (IL)-23 is a novel therapeutic target and mirikizumab is the first anti-IL-23 antibody approved for the treatment of moderately to severely active UC.

Areas covered: This review summarizes the pro-inflammatory effects of IL-23 and outlines the pharmacokinetics of mirikizumab. It provides a synopsis of the available phase II and phaseIII evidence for the efficacy and safety of mirikizumab in UC.

Expert opinion: The mirikizumab clinical development program demonstrated its superiority over placebo and its favorable safety profile in the treatment of UC. Its positioning in therapeutic algorithms remains to be fully understood but mirikizumab has proven efficacy in both advanced therapy (AT)-naïve and AT-experienced patients. The inclusion in the license of extended induction for non-responders as well as rescue intravenous dosing allows for flexibility in patient with limited primary response and secondary loss of response.

Introduction: Novel compounds have entered the triple-negative breast cancer (TNBC) treatment algorithm, namely immune checkpoints inhibitors (ICIs), PARP inhibitors and antibody-drug conjugates (ADCs). The optimization of treatment efficacy can be enhanced with the use of combination treatments, and the incorporation of novel compounds. In this review, we discuss the combination treatments under development for the treatment of TNBC.

Areas covered: The development of new drugs occurring in recent years has boosted the research for novel combinations to target TNBC heterogeneity and improve outcomes. ICIs, ADCs, tyrosine kinase inhibitors (TKIs), and PARP inhibitors have emerged as leading players in this new landscape, while other compounds like novel intracellular pathways inhibitors or cancer vaccines are drawing more and more interest. The future of TNBC is outlined in combination approaches, and based on new cancer targets, including many chemotherapy-free treatments.

Expert opinion: A large number of TNBC therapies have either proved clinically ineffective or weighted by unacceptable safety profiles. Others, however, have provided promising results and are currently in late-stage clinical trials, while a few have actually changed clinical practice in recent years. As novel, more and more selective drugs come up, combination strategies focusing the concept of synergy are fully warranted for the future.

Introduction: Gestational diabetes mellitus (GDM) has become the most common pregnancy medical complication, and its prevalence has increased in recent years. The GDM treatment primarily relies on adopting healthy eating habits, physical exercise, and insulin therapy. However, using probiotics to modulate the gut microbiota has been the subject of clinical trials as a promising therapeutic strategy for GDM management.

Areas covered: Due to the adverse effects of gut dysbiosis in women with GDM, strategies targeting the gut microbiota to mitigate hyperglycemia, low-grade inflammation, and adverse pregnancy outcomes have been explored. Probiotic supplementation may improve glucose metabolism, lipid profile, oxidative stress, inflammation, and blood pressure in women with GDM. Furthermore, decreased fasting blood glucose, insulin resistance, and inflammatory markers, such as TNF-α and CRP, as well as increased total antioxidant capacity, lipid profile modulation, and improved blood pressure in women with GDM, are some of the important results reported in the available literature.

Expert opinion: To fill the knowledge gap, further studies are needed focusing on modulating gut microbiota composition and metabolic activity and their systemic repercussions in GDM.

Introduction: While surgical resection is the cornerstone of treatment for resectable lung cancer, neoadjuvant/adjuvant chemotherapy has shown limited improvement in survival rates over the past decades. With the success of immune checkpoint inhibitors (ICIs) in advanced NSCLC, there is growing interest in their application in earlier stages of the disease. Recent approvals for neoadjuvant/adjuvant ICIs in stage II-IIIA NSCLC highlight this shift in treatment paradigms.

Areas covered: In this review, we aim to explore available data regarding alternative agents beyond the PD-(L)1 inhibitors, such as monoclonal antibodies against CTLA4, LAG3, TIGIT, antiangiogenic drugs, and novel therapies (antibody drug conjugates, bispecific antibodies) in neoadjuvant/perioperative regimens.

Expert opinion: Novel agents and combinations (with or without ICI or/and chemotherapy), guided by molecular profiling and immune phenotyping, showed promise in improving surgical and survival outcomes. Crucial is, also in early setting, to identifying biomarkers predictive of treatment efficacy in order to personalize neoadjuvant/perioperative treatment strategies.

Introduction: Cervical cancer remains one of the most common gynecologic malignancies worldwide. A disproportionate burden of cases occurs in developing countries due to inadequate screening and treatment. Even among patients adequately treated, in the presence of locally advanced or recurrent disease, outcomes tend to be poor. The introduction of biologic therapy into treatment has increased overall survival; however, a considerable opportunity still exists to improve current standards in treatment. Biologics have shown antitumor activity in multiple tumor types and are actively being pursued for the management of cervical cancer.

Areas covered: In this article, we will discuss the historical evolution of biologic therapy in cervical cancer including use of angiogenesis inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, and vaccines. We will review how these therapies have been integrated into current treatment recommendations and discuss ongoing investigations intended to improve clinical outcomes. We also postulate on persistent gaps in care.

Expert opinion: Biologic therapies have had a tremendous impact on our current approach to managing cervical cancer. We anticipate that significant more research and development will be committed to the continued investigation of biologics in cervical cancer in an effort to improve a historically difficult to treat malignancy.

Introduction: In children, ulcerative colitis (UC) is often more severe and extensive than in adults and hospitalization for acute exacerbations occurs in around a quarter of subjects. There is a need for effective drugs, which could avoid or reduce the use of corticosteroids which, especially in children, are burdened by a number of severe side effects. The introduction in therapy of monoclonal antibodies has completely changed the therapeutic scenario and the prognosis of the disease.

Areas covered: In this review, the use of the monoclonal antibodies directed against tumor necrosis factor (TNF)α or other inflammatory targets for the treatment of pediatric UC will be discussed. A search of the literature was done using the keywords 'pediatric,' 'ulcerative colitis,' 'inflammatory bowel disease,' 'monoclonal antibodies;' 'infliximab,' 'adalimumab,' 'golimumab,' vedolizumab," 'ustekinumab' and 'risankizumab.'

Expert opinion: The use of monoclonal antibodies has greatly increased in recent years in pediatric UC, both in patients who did not respond to conventional therapies, and, more often, as initial therapy. Thanks to therapeutic drug monitoring and to the availability of biologics with different targets, therapy has become more targeted and personalized, with a significant improvement in response, in quality of life, and with a good safety profile.