Human epidermal growth factor receptor 2 (HER2) amplification is an important molecular mechanism underlying carcinogenesis and is associated with various types of cancer. Although the advancement of HER2-targeted therapy has been the most pronounced in breast cancer, interest has emerged in exploring the efficacy of HER2-targeted therapies in gastrointestinal (GI) cancers. In particular, the addition of trastuzumab to first-line chemotherapy has improved the overall survival of patients with HER2-positive gastric or oesophagogastric junction cancer. Although subsequent trials involving lapatinib, ado-trastuzumab emtansine (T-DM1), and pertuzumab have failed to show significant survival benefits for HER2-positive gastric or oesophagogastric junction cancer, several trials are currently ongoing. HER2-targeted therapy has also been tested in patients with other GI cancers. Some combination therapies, such as trastuzumab plus pertuzumab, have shown promising results in single-arm phase II studies. Moreover, trials of novel anti-HER2 agents, including trastuzumab deruxtecan (T-DXd), tucatinib and margetuximab – which demonstrated improvement of clinical outcomes in breast cancer – are ongoing for GI cancers. In this review, we provide an overview of the current status of HER2-targeted therapies and focus on future perspectives for overcoming issues in the treatment of HER2-positive GI cancer.
Hodgkin lymphoma is a B-cell lymphoma that currently has a cure rate of ≥85% in patients with early-stage disease, using first-line chemotherapy followed by involved field radiotherapy. However, an unmet need remains in those with advanced and relapsed/ refractory Hodgkin lymphoma. In this review, we provide an overview of new and developing agents and discuss how these may re-shape clinical care strategies for patients with Hodgkin lymphoma. Overall, the emergence of targeted therapies such as brentuximab vedotin and immunotherapies such as nivolumab or pembrolizumab, provide new and exciting treatment options for patients. It is hoped that these will form single-agent and combination strategies that will re-shape the therapeutic landscape in Hodgkin lymphoma by (i) replacing elements of standard chemotherapy in low-risk patients to reduce toxicity and long-term complications, and (ii) by integrating into standardof-care therapies for advanced, high-risk or relapsed patients. Currently, brentuximab vedotin provides more robust and mature phase III clinical data in Hodgkin lymphoma, based on which, it appears reasonable to predict that brentuximab vedotin will form part of the first-line therapy for advanced Hodgkin lymphoma.
Despite technological advances, the prognosis and survival of acute myeloid leukemia (AML) adult patients remain low, compared with other hematologic malignancies. Some antigens detected by immunophenotyping may soon play a significant role in the pathophysiologic, prognostic, and overall survival (OS) rate of AML patients. Therefore, we conducted a systematic review and meta-analysis of PubMed, Scopus, Science Direct, Web of Science, and the Cochrane Library (using PRISMA guidelines). We analyzed 11 studies and 13 antigens, detected through the immunophenotyping of 639 patients. From them, twelve exhibited a negative impact with AML prognosis. The meta-analysis demonstrated a high expression of AML markers, which have been associated with a decrease in survival over 10 months (RR 2.55; IC 95%; 1.49–4.37) and over 20 months (RR 2.46; IC 95%; 1.75–3.45). Knowing that the expression of immunophenotypic markers, which are not used on a routine basis, might be able to influence disease behavior, looks promising. However, they have been associated with a poor prognosis as well as a decrease in survival. This may allow for different chemotherapeutical protocols, including future studies for new therapeutic targets.
