Antibody-Drug Conjugates in Ovarian Cancer: Promises and Challenges

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies globally, often detected at advanced stages which contribute to its high mortality rate. Recurrent and drug-resistant cases further complicate the therapeutic landscape, underscoring the urgent need for innovative treatment modalities. This review article addresses the transformative potential of antibody-drug conjugates (ADCs) as a novel therapeutic strategy for OC. ADCs, which combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs, offer a targeted approach to cancer cell elimination with minimized damage to normal tissues. Among ADCs that demonstrated promising activity in OC are mirvetuximab soravtansine, luveltamab tazevibulin, upifitamab rilsodotin, trastuzumab deruxtecan, sacituzumab govitecan, datopotamab deruxtecan and tisotumab vedotin. Here, we provide an overview of the ADCs' mechanism of action, highlight the specific tumor cell antigens targeted and present a comprehensive evaluation of clinical trials that have assessed the efficacy and safety of various ADC candidates in patients with OC

Whole-Body Composition Features by Computed Tomography in Ovarian Cancer: Pilot Data on Survival Correlations

Background: The primary objective of this study was to assess the associations of computed tomography (CT)-based whole-body composition values with overall survival (OS) and progression-free survival (PFS) in epithelial ovarian cancer (EOC) patients. The secondary objective was the association of body composition with chemotherapy-related toxicity. Methods: Thirty-four patients (median age 64.9 years; interquartile range 55.4–75.4) with EOC and thorax and abdomen CT scans were included. Clinical data recorded: age; weight; height; stage; chemotherapy-related toxicity; and date of last contact, progression and death. Automatic extraction of body composition values was performed by dedicated software. Sarcopenia was defined according to predefined cutoffs. Statistical analysis included univariate tests to investigate associations of sarcopenia and body composition with chemotoxicity. Association of body composition parameters and OS/PFS was evaluated by log-rank test and Cox proportional hazard model. Multivariate models were adjusted for FIGO stage and/or age at diagnosis. Results: We found significant associations of skeletal muscle volume with OS (p = 0.04) and PFS (p = 0.04); intramuscular fat volume with PFS (p = 0.03); and visceral adipose tissue, epicardial and paracardial fat with PFS (p = 0.04, 0.01 and 0.02, respectively). We found no significant associations between body composition parameters and chemotherapy-related toxicity. Conclusions: In this exploratory study, we found significant associations of whole-body composition parameters with OS and PFS. These results open a window to the possibility to perform body composition profiling without approximate estimations

PCSK9 inhibitors for treating dyslipidemia in patients at different cardiovascular risk: a systematic review and a meta-analysis

Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality, but many patients do not adequately reduce their LDL-C levels. Monoclonal antibodies targeting PCKS9 are currently in the advanced phase of development. We aimed to investigate the efficacy and safety of PCSK9 inhibitors in patients at different cardiovascular risk in a systematic review. Studies were searched on MEDLINE and EMBASE until January 2016. Differences in the outcomes among groups were expressed as mean differences, or pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. 22 RCTs and 8833 patients were included. Six studies were performed in patients affected by homozygous or heterozygous familial hypercholesterolemia, or with increased cardiovascular risk, two in patients with statin intolerance, three in statin-na\uc3\uafve patients, and 10 in patients unable to achieve LDL-C target with statin therapy. PCSK9 inhibitors were associated with a statistically significant reduction of LDL-C (mean = \ue2\u88\u9248.8%; 95% CI \ue2\u88\u9254.1, \ue2\u88\u9243.4; I2 = 94%) compared to control groups, and with a statistically significant reduction in death for any cause (OR = 0.34; 95% CI 0.17, 0.69; I2 = 0) and a favorable trend for cardiovascular events (OR = 0.79; 95% CI 0.61, 1.02; I2 = 0%). PCSK9 inhibitors reduce LDL-C concentration in every group explored. A significant reduction in death by all cause was observed in the PCSK9 inhibitors groups, compared with control groups, even in the short time frame studied