Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors’ immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research.

BACKGROUND: Neoadjuvant therapy with trastuzumab and pertuzumab (HP) combined with chemotherapy (ChT) is the standard of care in ≥ cT2cN0 or N+ HER2-positive early breast cancer (EBC). Although cardiotoxicity is a known adverse effect of anti HER2-therapy and anthracyclines, recently BERENICE final analysis showed cardiac safety of HP in combination with standard or dose-dense anthracycline-based ChT. However, real-world data is lacking, specifically in patients (pts) with identified cardiovascular (cv) risk factors. Our study aimed to evaluate cardiac safety of HP and anthracyclines in HER2+ EBC and explore potential impact of body mass index (BMI). METHODS: This retrospective analysis included HER2+ EBC pts receiving neoadjuvant HP and anthracycline- and taxane- based ChT, at our institution, between 2016 and 2021. Baseline clinical, demographic, histopathological and immunohistochemical features were reported. Pts were categorized as underweight (< 18.5kg/m2), normal (≥18.5;< 25kg/m2), overweight (≥25;< 30kg/m2) and obese (≥30kg/m2), according to basal BMI WHO categories. The primary objective was to evaluate cardiac safety, assessed by incidence of left ventricular ejection fraction (LVEF) declines (≥10% from baseline and to a value < 50%) and NYHA class III/IV heart failure. Univariate and multivariate logistic regression analysis were performed using BMI as a categorical variable. Safety data were compared in subgroup analyses for underweight/normal and overweight/obese pts. Statistics were performed with IBM™ SPSS software, version 23. RESULTS: Our analysis enrolled 112 female pts, with a median age of 54 years (30-78), including 22pts (19.6%) with ≥65years and 55 (49.1%) postmenopausal women. Most pts (n=89; 79.5%) had HR-positive disease. 44pts (39.3%) had stage II and 68pts (60.7%) had stage III disease. According to BMI, pts were classified as underweight (n=3; 2.7%), normal (n=40; 35.7%), overweight (n=47; 42%) and obese (n=22; 19.6%). No association was found between BMI and tumor stage (p=0.829), grade (p=0.753) and HR status (p=0.212). Other baseline cv risk factors were identified: former/active smoker (n=34;30.4%), diabetes (n=10;8.9%), hypertension (n=30;26.8%), and dyslipidemia (n=32;28.6%). Most pts had ≥2 cv risk factors (n=66;58.9%). Two diferent regimes were used FEC100-D+HP (2016-2019, n=84) and ddAC-wkPaclitaxel+HP (2020-2021, n=28). Overall, pCR was achieved in 62 pts (55.4%). Regarding cardiac safety evaluation, 4 pts (3.6%) experienced at least one LVEF decline ≥10% from baseline and to a value < 50%, including 3 pts that were overweight/obese. Declines were reversible in all pts, with recovery by next assessment. Two pts (1.8%) experienced one NYHA class III heart failure event. Both pts were overweight/obese and had another concomitant risk factor for cardiovascular disease. Both pts discontinued treatment. No statistically significant association was found between overweight/obesity and cardiac events (OR 1.26, 95%CI 0.22-7.20; p=0.792). Median follow-up duration was 39 months. No new safety signals were identified. CONCLUSION: Cardiac safety of neoadjuvant HP in combination with anthracyclines in HER2-positive EBC in our real-world data is consistent with previous studies. Despite most cardiac events occurred in overweight/obese pts, no statistically significant effect was found. Further studies are needed to evaluate cardiotoxicity in pts with cv risk factors and evaluate impact of therapeutic interventions. Citation Format: Diana Simão, Mariana Sardinha, Lúcia Gil, Alexandra Montenegro, José Mendes, Leonor Fernandes, Patrícia Winckler, Ricardo Luz, Sónia Oliveira. Neoadjuvant trastuzumab and pertuzumab in combination with anthracyclines in HER2-positive early breast cancer: real-world data on effect of body mass index in cardiac safety [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-55.

In recent years there has been an increase in the number of new cases of cancer. Malnutrition in cancer patients is a consequence of the increase in inflammatory cytokines associated with cancer, metabolic alterations, and concomitant inadequate availability of nutrients, due to anorexia caused by the disease and systemic treatments. Nutrition can guide both the growth and progress of inflammatory disorders and their prevention and treatment. Irrevocably, it is indispensable to pair the diet with physical activity, balance nutritional status and prime a healthy lifestyle. An increased understanding of the instruments linked to nutrients and the immune system is a breathtaking and exceptional field for the future. The gut microbiota is now known as a fundamental factor disturbing the host´s anti-cancer immunosurveillance and capacity to respond to immunotherapy. Diet is one of the most powerful modulators of microbiota, and therefore nutritional intervention could be used to increase host anti-cancer immunity. A rising body of data has also highlighted that the gut microbiota may have a constructive impact on cancer prevention or treatment, particularly via improved host immunosurveillance of cancer as well as patients ‘capacity to respond to chemotherapy or immunotherapy. The sway of nutrition on the immune system is a territory that remains under investigation. Nutrition and immunity are closely related. An expanded understanding of the mechanisms connected to nutrients and the immune system is a breathtaking and gifted field for the future.