Systemic therapies in advanced hepatocellular carcinoma: How do older patients fare?

Advanced hepatocellular cancer (HCC) is the fourth leading cause of cancer-related death globally and is most common in elderly patients with a peak incidence in the UK at ages 85-89 years. In addition to the well-established risk factors of alcohol and viral hepatitis B and C, rising obesity and associated non-alcoholic fatty liver disease is projected to contribute to increased incidence of advanced HCC in elderly patients. The management of advanced HCC is changing rapidly; for over a decade the multi-kinase inhibitor sorafenib has been the only treatment option that offered a proven survival advantage, but in the last 4 years other treatment options have emerged including other kinase inhibitors, and monoclonal antibodies targeting angiogenesis and immune checkpoint inhibitors. Recent clinical trials have recruited older patients with no maximum age exclusion criteria, and age has not been found to be predictive for treatment effect in subgroup analyses. Chronological age is an unreliable measure of fitness for treatment and frailty may be a more apt descriptor, but the lack of a unified assessment tool has limited its use in current practice. Development of unified frailty assessments and prospective large-scale studies of novel systemic therapies where age and frailty are evaluated would be informative.

Rivaroxaban thromboprophylaxis in ambulatory patients with pancreatic cancer: Results from a pre-specified subgroup analysis of the randomized CASSINI study.

BACKGROUND: Pancreatic cancer patients are at risk for venous thromboembolism (VTE); the value of thromboprophylaxis has not been definitively established. METHODS: This trial randomized cancer patients initiating a new regimen and at high risk for VTE (Khorana score ≥2) to rivaroxaban 10 mg or placebo up to day 180. This analysis examined the subset of pancreatic cancer patients. The primary efficacy endpoint was the composite of symptomatic deep-vein thrombosis (DVT), asymptomatic proximal DVT, any pulmonary embolism, and VTE-related death. The primary safety endpoint was International Society on Thrombosis and Haemostasis-defined major bleeding. RESULTS: In total, 49/1080 (4.5%) patients enrolled had baseline VTE on screening, with higher rates (24/362 [6.6%]) in pancreatic cancer and they were not randomized. Of 841 randomized patients, 273 (32.5%) had pancreatic cancer; 155/273 (57% in each arm) completed the double-blind period. The primary endpoint occurred in 13/135 (9.6%) patients in the rivaroxaban group and in 18/138 (13.0%) in the placebo group (hazard ratio [HR] = 0.70; 95% CI, 0.34-1.43; P = .328) in up-to-day-180 period and 5/135 (3.7%) patients receiving rivaroxaban and 14/138 (10.1%) receiving placebo in the intervention period (HR = 0.35; 95% CI, 0.13-0.97; P = .034). Major bleeding was similar (2 [1.5%] receiving rivaroxaban and 3 [2.3%] receiving placebo). Correlative biomarker studies demonstrated significant decline in D-dimer (weeks 8 and 16) in patients randomized to rivaroxaban compared to placebo (P < .01). CONCLUSIONS: In ambulatory pancreatic cancer patients, rivaroxaban did not result in significantly lower incidence of VTE or VTE-related death in the 180-day period. During the intervention period, however, rivaroxaban substantially reduced VTE without increasing major bleeding, suggesting benefit of rivaroxaban prophylaxis in this setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02555878.