Metronomic capecitabine versus best supportive care as second-line treatment in hepatocellular carcinoma: A retrospective study

Preliminary studies suggest that capecitabine may be safe and effective in HCC patients. The aim of this study was to retrospectively evaluate the safety and efficacy of metronomic capecitabine as second-line treatment. This multicentric study retrospectively analyzed data of HCC patients unresponsive or intolerant to sorafenib treatment with metronomic capecitabine or best supportive care (BSC).Median progression free survival was 3.1 months in patients treated with capecitabine (95%CI: 2.7-3.5). Median overall survival was 12.0 months (95% CI: 10.7-15.8) in patients receiving capecitabine, while 9.0 months (95% CI: 6.5-13.9) in patients receiving BSC. The result of univariate unweighted Cox regression model shows a 46% reduction in death risk for patients on capecitabine (95%CI: 0.357-0.829; p=0.005) compared to patients receiving BSC alone. After weighting for potential confounders, death risk remained essentially unaltered (45%; 95%CI: 0.354-0.883; p = 0.013). Metronomic capecitabine seems a safe second-line treatment for HCC patients in terms of management of adverse events, showing a potential anti-tumour activity which needs further evaluation in phase III studies

PSA Flare With Abiraterone in Patients With Metastatic Castration-Resistant Prostate Cancer

BACKGROUND: The aim of this study was to assess early serum prostate-specific antigen (PSA) changes in patients treated with abiraterone and to correlate those changes with clinical outcome. PATIENTS AND METHODS: We retrospectively evaluated 103 patients with castrate-resistant prostate cancer (CRPC) treated with compassionate use of abiraterone in Romagna, Italy. In these patients, serum PSA levels were monitored every 4 weeks, and a time course of serum PSA levels was obtained. The PSA flare phenomenon was evaluated. The log-rank test was applied to compare survival between groups of patients according to early PSA level changes. RESULTS: Of 103 patients, 43 (41.7%) had an immediate PSA response, whereas 9 (8.7%) had an initial PSA flare. Of the 9 patients with PSA flare, 5 attained a subsequent PSA response. The temporary PSA flare exceeded baseline values by a median of 19.7% (range, 5%-62.9%). The median PFS of the 9 patients in the PSA-flare group was higher compared with patients without the PSA flare (10.5 vs. 6.4 months; P = .0999) but was similar to the subgroup of patients with immediate PSA response (10.5 vs. 10.7 months; P = .7019). In the multivariate analysis, only the PSA response remained as a predictor of progression-free survival (PFS) (P < .0001) and overall survival (OS) (P = .0003), respectively. CONCLUSION: PSA flare occurs not infrequently in patients with CRPC who respond to abiraterone. Patients should be informed of this possible PSA flare phenomenon

Association of NOS3 and ANGPT2 Gene Polymorphisms with Survival in Patients with Hepatocellular Carcinoma Receiving Sorafenib: Results of the Multicenter Prospective INNOVATE Study

Purpose: After 10 years of clinical practice and research studies, there are still no validated prognostic or predictive factors of response to sorafenib for hepatocellular carcinoma (HCC). On the basis of the results of our two retrospective studies, we designed the multicenter INNOVATE study with the aim to validate the role of nitric oxide synthase 3 (NOS3) and ANGPT2 polymorphisms in patients with HCC treated with sorafenib [NCT02786342].Patients and Methods: This prospective multicenter study was conducted at 10 centers in Italy. All eligible patients received a continuous oral treatment with 400 mg of sorafenib twice daily. Genotyping analysis was performed for NOS3 (rs2070744) and ANGPT2 SNPs (rs55633437). The primary outcome was progression-free survival (PFS), whereas secondary outcomes included overall survival (OS) and disease-control rate.Results: A total of 165 patients were enrolled between March 2016 and June 2018. NOS3 rs2070744 CC/CT genotypes were significantly associated with a higher median PFS (5.9 months vs. 2.4 months; HR = 0.43; P = 0.0007) and OS (15.7 months vs. 8.6 months; HR = 0.38; P &lt; 0.0001) compared with TT genotype. There was no statistically significant association between ANGPT2 rs55633437 TT/GT genotypes and PFS (2.4 months vs. 5.7 months; HR = 1.93; P = 0.0833) and OS (15.1 months vs. 13.0 months; HR = 2.68; P = 0.55) when compared with the other genotype. Following adjustment for clinical covariates, multivariate analysis confirmed NOS3 as an independent prognostic factor for PFS (HR = 0.50; P = 0.0128) and OS (HR = 0.29; P = 0.0041).Conclusions: The INNOVATE study met the primary endpoint, confirming that patients with advanced HCC with NOS3 rs2070744 CC/CT genotypes had a better prognosis with respect to TT genotype patients

Outcomes of a 3-year prospective surveillance in individuals at high-risk for pancreatic cancer

Introduction: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a pre-clinical stage. In 2015 the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms seven years after the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) inception focusing on individuals with at least a 3-year follow-up or developing events before. Methods: HRI (subjects with family history or mutation carriers with/without family history were enrolled in 18 Centers. They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). Results: During the study period (June 2015 - September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/pre-malignancy-related events, and represented the study population. Median age was 51 (IQR 16). Familial PC cases (FPC) accounted for 81.4% of HRI, and individuals with pathogenic variant (PV) for 18.6%. Malignant (n=8) and pre-malignant (1 PanIN3) lesions were found in nine individuals. Five of these 8 cases occurred in PV carriers, four in FPC cases (two tested negative at germline testing, and two others were not tested). Three of the 8 PC were Stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5% and 3%, respectively. Median overall and disease-free survival of resected PC patients were 18 and 12 months (95%CI not computable). Considering HRI who underwent baseline imaging, six pancreatic neuroendocrine neoplasms (one resected) and one low-yield surgery (low-grade mixed-IPMN) were also reported. Conclusion: PC surveillance in a fully public healthcare system is feasible, safe, and leads to early PC or pre-malignant lesions diagnoses, mostly at baseline but also over time