Cristiana Sessa

Objectives: The objective of this single-site retrospective study was to assess the association between Computed Tomography (CT)-based whole-body composition values with dose reduction in patients with a diagnosis of epithelial ovarian cancer (EOC) treated with poly ADP-ribose polymerase (PARP) inhibitors (PARPi). Methods: Forty-eight patients (median age 61 years; interquartile range 53–68.5) with EOC who had a thorax and abdomen CT scan (performed before starting PARPi) were enrolled. Recorded clinical data included age, weight, height, stage, start and end date of PARPi, dose reduction, premature discontinuation of therapy, date of last contact, progression, and death. Body composition values were automatically extracted by dedicated software. Given the exploratory nature of the study, the statistical analysis combined univariate assessments (univariate logistic regression) used to evaluate the individual effect of each variable on the probability of dose reduction, with a classification tree approach—a data-driven machine learning method considering all variables simultaneously as covariates. This integrated strategy was designed to identify empirical cut-offs defining body composition profiles associated with increased risk of toxicity. Results: Univariate logistic regression showed no statistically significant effect of body composition variables on the probability of dose reduction. Due to the complexity of variable relations, a machine-learning approach with a classification tree showed that SKM (skeletal muscle) was the sole body composition variable significantly associated with dose reduction. Specifically, there was a higher risk of dose reduction with SKM values ≥ 7506 cm³ and < 8650 cm³ (p = 0.0118). Conclusions: In this exploratory study, a significant association of whole-body composition parameters (SKM) with dose reduction was observed in patients with a 7506 cm³ ≤ SKM < 8650 cm³. If confirmed in larger cohorts, these findings could help clinicians identify patients who might benefit from an upfront reduced PARPi dose.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care. Here, the essential requirements to treat ovarian cancer patients are described. Ovarian cancer patients continue to have low cure rates with wide variation in treatment and care in Europe and beyond. They require complex treatment that should be carried out in specialised ovarian/gynaecological cancer centres by professionals with the appropriate expertise interacting in a multidisciplinary team. Such centralisation is still not well established in many European countries. A patient-centred pathway from diagnosis through treatment to survivorship, managed in dedicated centres, is key to achieving optimal care and a successful clinical outcome.

Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. Due to the lack of effective screening and early detection strategies, many patients with OC are diagnosed with advanced dise

Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents. These drugs have been extensively studied both in solid and hematologic malignancies, leading to substantial improvement in the therapeutic landscape for several tumors. Despite no ADC have been yet approved for the treatment of gynecological malignancies, some agents have shown promising results and might have the potential to become part of the standard of care. Among them, mirvetuximab soravtansine has shown activity in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent and in combination. Tisotumab vedotin is active in patients with pre-treated cervical cancer, and further investigation is ongoing. The purpose of this review is to summarize the structural and functional characteristics of ADCs and analyze the most recent and promising data regarding the clinical development of ADCs in gynecological malignancies. The available data on the efficacy of the more studied ADCs in ovarian, endometrial, and cervical cancers will be discussed along with toxicities of special interest, the mechanisms of resistance, and future possible drugs combination.

Targeting the inherent vulnerability of cancer cells with an impaired DNA Damage Repair (DDR) machinery, Poly-ADP-Ribose-Polymerase (PARP) inhibitors have yielded significant results in several tumor types, eventually entering clinical practice for the treatment of ovarian, breast, pancreatic and prostate cancer. More recently, inhibitors of other key components of DNA repair, such as ATR, CHK1 and WEE1, have been developed and are currently under investigation in clinical trials. The inhibition of DDR inevitably induces on-target and off-target adverse events. Hematological and gastrointestinal toxicities as well as fatigue are common with all DDR-targeting agents, while other adverse events are drug specific, such as hypertension with niraparib and transaminase elevation with rucaparib. Cases of pneumonitis and secondary hematological malignancies have been reported with PARP inhibitors and, despite being overly rare, they deserve particular attention due to their severity. Safety also represents a crucial issue for the development of combination regimens incorporating DDR-targeting agents with other treatments, such as chemotherapy, anti-angiogenics or immunotherapy. As such, overlapping and cumulative toxicities should be considered, especially when more than two classes of drugs are combined. Here, we review the safety profile of DDR-targeting agents when used as single agents or in combination and we provide principles of toxicity management.

Background: The European Patients' Academy on Therapeutic Innovation Switzerland (EUPATI CH) was established as an association in 2016 with the mission to improve patient empowerment in Switzerland, raise public awareness of EUPATI's education material, and foster multi-stakeholder partnerships in order to promote public involvement in all aspects of medicines research and development (R&D). In order to achieve its goal of improving patient involvement (PI) in all processes of medicines R&D in Switzerland and to obtain guidance and recommendations for future activities, EUPATI CH initiated a multi-stakeholder survey on PI experiences, hurdles, and best practices. The survey enabled EUPATI CH to obtain and analyze the views of various stakeholders and shape its workplan.Methods: Data collection occurred between January and July 2019 using a survey and semi-structured interviews with individual stakeholders from different groups. The online survey responses were analyzed using quantitative methods and the interviews were analyzed using qualitative methods.Results: The online survey was completed by 55 respondents (10%), and the semi-structured interviews were conducted with 14 stakeholders. Respondents to the online survey were patient representatives (45%), researchers from academia (25%), individuals from the pharmaceutical industry (9%), healthcare professionals (23%), and representatives from government agencies (6%). Some respondents were also members of EUPATI CH. Thirty-eight percent of respondents consider PI in Switzerland to be limited or absent. They identified the main barriers to PI as, first and foremost, a lack of funds and human resources (65%), followed by a lack of information and a lack of education on how to become a patient advocate (21%), a lack of collaboration with other stakeholders (16%), and a lack of adequate resources. Respondents' expectations of EUPATI CH's role in supporting PI were to provide education for active PI and improve networking and collaboration among stakeholders.Conclusions: EUPATI CH's multi-stakeholder research identified some of the difficulties in promoting PI in medicines R&D in Switzerland, in particular the complex collaboration among stakeholders and a lack of funds, human resources, and knowledge. To respond to these difficulties, EUPATI CH has begun preparing a basic training course for patients that is adapted to Switzerland.