Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial.

PURPOSE: Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting BRCA mutation and/or BRCAness phenotype. METHODS: A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m2 given once every 3 weeks (arm A) in BRCA 1/2 mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population. RESULTS: Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months (P = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B (P = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 v 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to BRCA mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy. CONCLUSION: Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.

Neoadjuvant systemic treatment in breast cancer surgery: is it always worth it?

BACKGROUND: Surgeons perspective of breast cancer (BC) treatment has deeply changed in recent time. We investigated survival outcomes of BC patients who underwent Neoadjuvant systemic treatment (NAT) before surgery and to assess the role of NAT in determining possible prognosis. METHODS: We retrospectively analyzed a total of 2372 BC patients consecutively enrolled in our prospective institutional database. Seventy-eight patients over 2372 reached the inclusion criteria and underwent surgery after NAT. RESULTS: After NAT, the 50% of luminal-B-HER2+ and the 53% of HER2+ had a pathological complete response (pCR) and only 18.5% of the TNs had a pCR. NAT significantly changed lymph node status (P=0.05). All women with pCR are still alive (No-pCR 0.732 CI: 0.589-0.832; yes-pCR 1.000 CI: 1.00-1.00; P=0.02). The molecular biology of the tumor, after NAT, is strictly related to survival both for 3- and 5-years OS. A triple negative BC have the worst prognosis (HER2+ 0.796 CI: 0.614-1; Luminal-A: 1 CI:1-1; LuminalB-HER2 -: 0.801 CI: 0.659-0975; LuminalB-HER2+: 1 CI:1-1; TN 0.542 CI: 0.372-0789, P=0.002). CONCLUSIONS: We can state that, based on our experience, we can consider safe and effective conservative interventions following neoadjuvant therapy. An adequate selection of patients is crucial. It is also clear how the planning of the therapeutic path plays a key role in an interdisciplinary context. NAT is a source of hope for the future both for the identification of new predictors of prognosis and in the field of research, for the development of new drugs.

Consensus statements and treatment algorithm to guide clinicians in the selection of maintenance therapy for patients with newly diagnosed, advanced ovarian carcinoma: Results of a Delphi study.

INTRODUCTION: Standard treatment of newly diagnosed, advanced ovarian carcinoma (OC) consists of cytoreductive surgery followed by platinum-based chemotherapy with or without bevacizumab. Maintenance therapy with PARP inhibitors and olaparib-bevacizumab has recently shown to significantly improve progression-free survival in the first-line setting. Some practical aspects of maintenance therapy, however, are still poorly defined. AIM OF THE STUDY: To provide guidance to clinicians in the selection of maintenance therapy for newly diagnosed, advanced ovarian carcinoma. METHODS: A board of six gynecologic oncologists with expertise in the treatment of OC in Italy convened to address issues related to the new options for maintenance treatment. Based on scientific evidences, the board produced practice-oriented statements. Consensus was reached via a modified Delphi study that involved a panel of 22 experts from across Italy. RESULTS: Twenty-seven evidence- and consensus-based statements are presented, covering the following areas of interest: use of biomarkers (BRCA mutations and presence of homologous recombination deficiency); timing and outcomes of surgery; selection of patients eligible for bevacizumab; definition of response to treatment; toxicity and contraindications; evidence of synergy of bevacizumab plus PARP inhibitor. Two treatment algorithms are also included, for selecting maintenance therapy based on timing and outcomes of surgery, response to platinum-based chemotherapy and biomarker status. A score for the assessment of response to chemotherapy is proposed, but its validation is ongoing. CONCLUSIONS: We provide here consensus statements and treatment algorithms to guide clinicians in the selection of appropriate and personalized maintenance therapy in the first-line setting of advanced OC management.

Impact of psychosocial, behavioral and lifestyle factors on subjective cognitive complaints and perceived quality of life in a large cohort of Italian breast cancer patients.

The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive complaints in breast cancer patients (37%) compared to a representative sample of women in the same age group without an oncological diagnosis (p < 0.001). Moreover, breast cancer patients showed significantly lower levels of cognitive reserve (p < 0.05) and worse sleep quality (p < 0.01) compared to age-matched controls. Further analysis revealed that breast cancer patients reporting subjective cognitive complaints differed significantly from breast cancer patients without subjective cognitive complaints on measures of perceived cognitive abilities (p < 0.001) and on the impact of cognitive difficulties on perceived quality of life (p < 0.01). Future studies are needed to examine behavioral directed interventions to prevent subjective cognitive deficits in breast cancer patients.

Comparison between male and female breast cancer survival using propensity score matching analysis.

Male breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management.

Direct comparison of three different mathematical models in two independent datasets of EUSOMA certified centers to predict recurrence and survival in estrogen receptor-positive breast cancer: impact on clinical practice.

PURPOSE: Prediction algorithms estimating survival rates for breast cancer (BC) based upon risk factors and treatment could give a help to the clinicians during multidisciplinary meetings. The aim of this study was to evaluate accuracy and clinical utility of three different scores: the Clinical Treatment Score Post-5 Years (CTS5), the PREDICT Score, and the Nottingham Prognostic Index (NPI). METHODS: This is a retrospective cohort analysis conducted on prospectively recorded databases of two EUSOMA certified centers (Breast Unit of Trieste Academic Hospital and of Cremona Hospital, Italy). We included patients with Luminal BC undergone to breast surgery between 2010 and 2015, and subsequent endocrine therapy for 5 years for curative intent. RESULTS: A total of 473 patients were enrolled in this study. ROC analysis showed fair accuracy for NPI, good accuracy for PREDICT, and optimal accuracy for CTS5 (AUC 0.7, 0.76, and 0.83, respectively). The three scores seemed strongly correlated in Spearman's rank correlation coefficient analysis. PREDICT partially overestimated OS in patients undergone to mastectomy, and in pT3-4, G3 tumors. Considering DRFS as a surrogate of OS, CTS5 showed women in intermediate and high risk class had shorter OS too (respectively p = 0.001 and p < 0.001). Combining scores does not improve prognostication power. CONCLUSION: Mathematical models may help clinicians in decision making (adjuvant therapies, CDK4/6i, genomic test's gray zones). CTS5 has the higher prognostic accuracy in predicting recurrence, while score predicting OS did not show substantial advances, proving that pN, G, and pT are still the most important variables in predicting OS.

The Extracellular Matrix Influences Ovarian Carcinoma Cells' Sensitivity to Cisplatinum: A First Step towards Personalized Medicine.

The development of personalized therapies for ovarian carcinoma patients is still hampered by several limitations, mainly the difficulty of predicting patients' responses to chemotherapy in tumor cells isolated from peritoneal fluids. The main reason for the low predictive power of in vitro assays is related to the modification of the cancer cells' phenotype induced by the culture conditions, which results in changes to the activation state and drug sensitivity of tumor cells compared to their in vivo properties. We have defined the optimal culture conditions to set up a prognostic test to predict high-grade serous ovarian carcinoma (HGSOC) patients' responses to platinum chemotherapy. We evaluated the effects of hyaluronic acid (HA) and fibronectin matrices and the contribution of freezing/thawing processes to the cell response to platinum-based treatment, collecting spheroids from the ascitic fluids of 13 patients with stage II or III HGSOC. Our findings indicated that an efficient model used to generate predictive data for in vivo sensitivity to platinum is culturing fresh spheroids on HA, avoiding the use of previously frozen primary tumor cells. The establishment of this easy, reproducible and standardized testing method can significantly contribute to an improvement in therapeutic effectiveness, thus bringing the prospect of personalized therapy closer for ovarian carcinoma patients.