Trastuzumab deruxtecan in breast cancer.

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) consisting of a humanised, anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody covalently linked to a topoisomerase I inhibitor cytotoxic payload (DXd). The high drug-to-antibody ratio (8:1) ensures a high DXd concentration is delivered to target tumour cells, following internalisation of T-DXd and subsequent cleavage of its tetrapeptide-based linker. DXd's membrane-permeable nature enables it to cross cell membranes and potentially exert antitumour activity on surrounding tumour cells regardless of HER2 expression. T-DXd's unique mechanism of action is reflected in its efficacy in clinical trials in patients with HER2-positive advanced breast cancer (in heavily pretreated populations and in those previously treated with a taxane and trastuzumab), as well as HER2-low metastatic breast cancer. Thus, ADCs such as T-DXd have the potential to change the treatment paradigm of targeting HER2 in metastatic breast cancer, including eventually within the adjuvant/neoadjuvant setting.

Recent advances in the management of pulmonary arterial hypertension: lessons from the upfront combination of ambrisentan and tadalafil.

INTRODUCTION: The sixth World Symposium of Pulmonary Hypertension (sixth WSPH) brought to the forefront for the first time the value of earlier, aggressive management with an upfront oral combination in patients with pulmonary arterial hypertension (PAH) of low or intermediate risk. This was prompted by results from the AMBITION study (ambrisentan + tadalafil). A literature search was conducted to collect all evidence provided by upfront treatment with this combination, as well as other combinations under investigation at the time the manuscript was prepared. AREAS COVERED: The value of an upfront oral combination with ambrisentan and tadalafil is reviewed on the basis of topics discussed at the sixth WSPH, such as evidence in different PAH etiologies, according to risk stratification and in so-called 'atypical' patients where monotherapy is still recommended. Evidence in clinical practice is also reviewed. New evidence about the value of the upfront oral combination is also commented. Finally, tendencies in primary endpoints to assess the effect of PAH-targeted therapies (time to clinical worsening and hemodynamics) and their value are also reviewed. EXPERT OPINION: All above-mentioned aspects are put into perspective with regard to the impact of new advances on improving PAH management in clinical practice.

Endometriotic Pain Is Associated with Adenomyosis but Not with the Compartments Affected by Deep Infiltrating Endometriosis.

BACKGROUND: The identification of presurgical clinical markers may be helpful to allow the staging of endometriosis severity. It has been suggested that pain characteristics orientate the gynecologist about the anatomical involvement of endometriosis. The study was performed to analyze the correlation between pain symptoms and the anatomical location of endometriosis. METHODS: One hundred fifty-five consecutive patients with a complete removal of deep infiltrating endometriosis (DIE) were included. Prior to surgery, data on patient and disease characteristics were obtained. The intensity of the pain symptoms was registered using a Visual Analogue Scale. The endometriotic lesions were categorized according to the Enzian morphological classification. Correlation and multivariate analysis were performed to assess the potential associations between pain characteristics (dysmenorrhea, pelvic pain, dyschezia, dyspareunia or dysuria) and the location of endometriosis or other disease-related characteristics (hematuria, rectal bleeding or adenomyosis). RESULTS: Pelvic pain was significantly associated with the presence of adenomyosis. Dyschezia was correlated with rectal bleeding and dysuria with the presence of hematuria. No relationship was found between other kinds of pain and the morphological location of endometriosis or other disease-related characteristics. CONCLUSION: Our data suggest that pelvic pain is correlated with the presence of adenomyosis in women with DIE. Further studies are required.