Datopotamab deruxtecan: A novel antibody drug conjugate for triple-negative breast cancer.

Triple negative breast cancer (TNBC) represents the breast cancer subtype with least favorable outcome because of the lack of effective treatment options and its molecular features. Recently, ADCs have dramatically changed the breast cancer treatment landscape; the anti-TROP2 ADC Sacituzumab Govitecan has been approved for treatment of previously treated, metastatic TNBC patients. The novel ADC Datopotecan-deruxtecan (Dato-DXd) has recently shown encouraging results for TNBC. In the current paper, we summarize and discuss available data regarding this TROP-2 directed agent mechanism of action and pharmacologic activity, we describe first results on efficacy and safety of the drug and report characteristics, inclusion criteria and endpoints of the main ongoing clinical trials.

Safety evaluation of Datopotamab deruxtecan for triple-negative breast cancer: a meta-analysis.

BACKGROUND: TROP-2 is emerging as a valid and fruitful strategy in triple-negative breast cancer (TNBC) patients, and several agents are currently under evaluation, including Datopotamab deruxtecan (Dato-DXd). RESEARCH DESIGN AND METHODS: Herein, we performed a meta-analysis aimed to evaluate any grade adverse events, grade 3-4 adverse events, dose reduction, and serious adverse events in TNBC patients treated with Dato-DXd in clinical trials. RESULTS: The pooled results suggests that Dato-DXd is associated with a favorable safety profile: while any grade treatment-related toxicities were common, grade 3-4 events were not particularly frequent and mainly represented by stomatitis (13.88%; 95% CI, 10.68 - 17.09). CONCLUSIONS: These findings may help to comprehensively define the safety profile of Dato-DXd and to assist in the design of future clinical trials in this setting.

Electrochemotherapy for solid tumors: literature review and presentation of a novel endoscopic approach.

BACKGROUND: Electrochemotherapy (ECT) is a minimally invasive and safe treatment gaining positive and long-lasting antitumoral results that are receiving the attention of the scientific community. It is a local treatment that combines the use of electroporation and the administration of cytotoxic drugs to induce cell death in the target tissue. ECT is largely used for the treatment of cutaneous and subcutaneous lesions, and good results have been reported for the treatment of deep visceral tumors. The latest literature review is provided. Moreover, in line with its development for the treatment of visceral tumors in this article, we describe a novel approach of ECT: endoscopic treatment of colorectal cancer. Endoscopic ECT application was combined with systemic chemotherapy in the treatment of obstructing rectal cancer without prospective surgery. A good response after ECT was described: concentric involvement of the rectum was reduced, and no stenosing lesions were detected. CONCLUSIONS: Clinical studies have demonstrated that ECT is a very effective treatment for tumors of different histologic types and localizations. Endoscopic treatment for gastrointestinal cancer is an innovative application of ECT. The combination of systemic treatment and ECT was safe and highly effective in the treatment of colorectal cancer, especially when obstructive, giving the patient a significant gain in quality of life.

The Growing Skyline of Advanced Hepatocellular Carcinoma Treatment: A Review.

Hepatocellular carcinoma (HCC) is the main type of liver cancer. In the majority of cases, HCC is diagnosed at the advanced stage, leading to poor prognosis. In recent years, many efforts have been devoted to investigating potential new and more effective drugs and, indeed, the treatment armamentarium for advanced HCC has broadened tremendously, with targeted- and immune-therapies, and probably the combination of both, playing pivotal roles. Together with new established knowledge, many issues are emerging, with the role of neoadjuvant/adjuvant settings, the definition of the best transitioning time from loco-regional treatments to systemic therapy, the identification of potential predictive biomarkers, and radiomics being just some of the topics that will have to be further explored in the next future. Clearly, the current COVID-19 pandemic has influenced the management of HCC patients and some considerations about this topic will be elucidated.

The Challenge of ICIs Resistance in Solid Tumours: Could Microbiota and Its Diversity Be Our Secret Weapon?

The human microbiota and its functional interaction with the human body were recently returned to the spotlight of the scientific community. In light of the extensive implementation of newer and increasingly precise genome sequencing technologies, bioinformatics, and culturomic, we now have an extraordinary ability to study the microorganisms that live within the human body. Most of the recent studies only focused on the interaction between the intestinal microbiota and one other factor. Considering the complexity of gut microbiota and its role in the pathogenesis of numerous cancers, our aim was to investigate how microbiota is affected by intestinal microenvironment and how microenvironment alterations may influence the response to immune checkpoint inhibitors (ICIs). In this context, we show how diet is emerging as a fundamental determinant of microbiota's community structure and function. Particularly, we describe the role of certain dietary factors, as well as the use of probiotics, prebiotics, postbiotics, and antibiotics in modifying the human microbiota. The modulation of gut microbiota may be a secret weapon to potentiate the efficacy of immunotherapies. In addition, this review sheds new light on the possibility of administering fecal microbiota transplantation to modulate the gut microbiota in cancer treatment. These concepts and how these findings can be translated into the therapeutic response to cancer immunotherapies will be presented.

Immunotherapy in head and neck cancer: The great challenge of patient selection.

The development of immune checkpoint inhibitors (ICIs) revolutionized the therapeutic landscape in head and neck cancer. However, the majority of patients present primary resistance to ICIs and do not benefit from use of these agents, highlighting the need of developing predictive biomarkers to better determine who will benefit from treatment with ICIs. Patient's related clinical characteristics, disease related features, pathological and molecular factors, as well as emerging immune predictive biomarkers can be considered for the selection of those patients who would be the best candidate for immunotherapy. We examined these factors, emerging from the results of currently available studies in head and neck squamous cell carcinoma (HNSCC), in order to provide a useful tool which could assist the oncologist in their clinical practice.

Electrochemotherapy as Promising Treatment Option in Rare Recurrent Cutaneous Neoplasm of the Scalp: Case Report of an Elderly Patient.

BACKGROUND: Atypical fibroxanthoma (AFX) is a tumor that commonly presents on the head or neck in older individuals. Making a definitive diagnosis of AFX is challenging, and frequently, it is hard to distinguish from pleomorphic dermal sarcoma (PDS). There are no clear recommendations regarding the treatment of AFX, but an extensive surgery is actually considered the best option. Electrochemotherapy (ECT) is a novel therapeutic modality of local treatment in which the application of electrical pulses, enhancing cell membrane permeability, allows greater intracellular accumulation of chemotherapy drugs in the skin or subcutaneous tumors. CASE REPORT: We report a case of a 78-year-old male affected by a red, ulcerative, dermal, scalp nodule, which was treated with ECT with a complete clinical response. We have also reported literature data on this topic. RESULTS: In this case, ECT showed to be an effective and safe treatment for recurrent neoplasms of the head and neck, considering the complete response obtained and the absence of disease relapse after two years. CONCLUSION: To the best of our knowledge, this is the first case report that shows great clinical results using ECT after surgery in relapsed AFX/PDS. However, more studies are needed to confirm our results.

Clinical Impact of Highly Purified, Whey Proteins in Patients Affected With Colorectal Cancer Undergoing Chemotherapy: Preliminary Results of a Placebo-Controlled Study.

Background and Aims: Sarcopenia, the loss of both lean body and skeletal muscle mass, may interfere in cancer patients outcome. As investigated, whey proteins could prevent the onset of sarcopenia. We have conducted a study to evaluate the effects of whey protein in colorectal cancer patients, undergoing 5-fluorouracil-based chemotherapy. Methods: After written informed consent, patients were blind randomized 1:1 to whey protein (ProLYOtin; arm A) versus placebo (arm B). The patients were assessed both physically and nutritionally before chemotherapy and after 3 (T2) and 6 months (T3) by body impedance assessment, L3-computed tomography scan, Mini Nutritional Assessment (MNA), and Malnutrition Universal Screening Tool (MUST) tests. Results: Forty-seven patients were included in this preliminary analysis. Baseline characteristics were well balanced between the 2 arms. During chemotherapy, 33 patients were reevaluated: anthropometric parameters (lean body mass from 68.5% to 71.2% vs 68.7% to 66.3%, and sarcopenia from 84% to 54% and 83% to 77% from baseline to T2 evaluation in arms A and B, respectively), nutritional status (MNA >24 = 100% [A] vs 73.7% [B]), and toxicity (no adverse effects in 86% [A] vs 29% [B] and 94% [A] vs 29% [B] for hematological and gastrointestinal toxicities, respectively) resulted to be significantly different. At univariate analysis, a condition of malnutrition risk according to MUST (relative risk [RR] = 7.5, P = .02) or MNA (RR = 1.45, P = .02) and ProLYOtin intake (RR = 0.12, P = .01) were found to be significantly predictive of chemotherapy toxicity. Conclusions: At present, our study shows how whey protein could be an important therapeutic option to improve nutritional status, and particularly to prevent severe toxicity during chemotherapy.