Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer. A real world experience from the MITO group.

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.

Epithelial ovarian cancer is the most lethal gynecologic malignancy. In most women, it is diagnosed at an advanced stage, which largely explains the poor prognosis of this malignancy. Germline mutations of the genes BRCA1 and BRCA2, which encode proteins essential for the repair of double-strand DNA breaks through homologous recombination, lead to increased cancer predisposition. BRCA mutations are present in approximately 14% of epithelial ovarian cancers. Somatic BRCA mutations have also been described. Current first-line treatment of high-grade epithelial ovarian cancer includes debulking surgery followed by combination chemotherapy, usually carboplatin and paclitaxel. Ovarian cancer is highly sensitive to chemotherapy, in particular to platinum drugs. Most patient will achieve remission with initial chemotherapy, but most will eventually experience disease recurrence. Targeted therapies, including the anti-angiogenic agent bevacizumab and oral poly (ADP-ribose) polymerase (PARP) inhibitors, have been recently approved for the treatment of ovarian cancer, based on the results from randomized clinical trials showing significant benefits in terms of progression-free survival, with acceptable tolerability and no detrimental effects on quality of life. Olaparib, the first PARP inhibitor to be granted approval, is currently indicated as maintenance monotherapy in ovarian cancer patients with relapsed disease and mutated BRCA who have achieved a complete or partial response to platinum-based chemotherapy. The analysis of BRCA mutational status has, therefore, also become crucial for therapeutic decisions. Such advances are making personalized treatment of ovarian cancer feasible. Here we briefly review treatments for platinum-sensitive, high-grade serous epithelial ovarian cancer that are currently available in Italy, with a focus on targeted therapies and the relevance of BRCA mutational analysis. Based on the evidence and on current guidelines, we propose strategies for the tailored treatment of patients with relapsed ovarian cancer that take into account BRCA mutational status and the treatment received in the first-line setting.

Ovarian cancer represents one of the most aggressive female tumors worldwide. Over the decades, the therapeutic options for the treatment of ovarian cancer have been improved significantly through the advancement of surgical techniques as well as the availability of novel effective drugs able to extend the life expectancy of patients. However, due to its clinical, biological and molecular complexity, ovarian cancer is still considered one of the most difficult tumors to manage. In this context, several studies have highlighted how a multidisciplinary approach to this pathology improves the prognosis and survival of patients with ovarian cancer. On these bases, the aim of the present review is to present recent advantages in the diagnosis, staging and treatment of ovarian cancer highlighting the benefits of a patient-centered care approach and on the importance of a multidisciplinary team for the management of ovarian cancer.

Background: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. Patients and methods: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophilto-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. Results: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR !3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII !884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII þ PD-L1 þ LDH and SII þ PD-L1 combinations. Conclusion:The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.

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Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p < 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p < 0.001), body image (p < 0.001), future perspective (p < 0.001), well-being (p = 0.001), and reductions in fatigue (p < 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p < 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m 2). The 14-item PREDIMED questionnaire was used to analyse adherence to the Med-Diet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23.