PF702 USE OF THE THROMBOPOIETIN RECEPTOR AGONIST LUSUTROMBOPAG FOR THROMBOCYTOPENIA IN PATIENTS WITH HEPATOCELLULAR CARCINOMA UNDERGOING PLANNED INVASIVE PROCEDURES: INTEGRATED ANALYSIS OF 2 TRIALS

Abstract

Background:Patients with hepatocellular carcinoma may require repeated invasive procedures, such as ablation and embolization. Thrombocytopenia complicates management of chronic liver disease and may delay the ability to perform invasive procedures. Platelet transfusions can be administered but have disadvantages, including short duration and risk of allergic reactions and infection. Lusutrombopag is an oral, small molecule thrombopoietin receptor agonist approved in Japan and US for improvement of thrombocytopenia, and in EU for severe thrombocytopenia, associated with chronic liver disease in patients undergoing a planned invasive procedures.Aims:To assess lusutrombopag efficacy and safety compared to placebo as an alternative to platelet transfusion in patients with hepatocellular carcinoma and those with other chronic liver disease diagnoses without hepatocellular carcinoma.Methods:Two similar Phase 3 multicenter, randomized, double‐blind, placebo‐controlled trials were conducted (L‐PLUS 1 [JapicCTI‐132323] in Japan and L‐PLUS 2 [NCT02389621] globally). Adults with chronic liver disease and platelet counts <50x109/L at baseline were randomized to receive lusutrombopag 3 mg once daily or placebo for up to 7 days prior to an invasive procedure scheduled 9–14 days after randomization. Platelet transfusion was mandated if the platelet count remained <50x109/L no more than 2 days prior to the procedure. The efficacy endpoint based on the per‐protocol population was the proportion of patients who required no platelet transfusion prior to the invasive procedure and no rescue therapy for bleeding from randomization through 7 days after the invasive procedure.Results:312 patients were randomized. Of the 270 patients in the per‐protocol population, 95 had hepatocellular carcinoma and 175 had other chronic liver disease. For subjects with hepatocellular carcinoma, the mean age was 65.6 years, 61.1% were male, and 88.4% of the primary invasive procedures were liver‐related. The efficacy endpoint was met for 68.0% of patients with hepatocellular carcinoma who received lusutrombopag versus 8.9% of patients with hepatocellular carcinoma who received placebo. This was compared to 77.0% and 21.6%, respectively, among patients with other chronic liver disease diagnoses (Figure). In patients with hepatocellular carcinoma, platelet counts remained above 50x109/L for a median 16.6 days in the lusutrombopag group, compared to 3.8 days for placebo. One patient treated with lusutrombopag experienced treatment‐emergent portal vein thrombosis but never reached a platelet count >200x109/L.Summary/Conclusion:In this post‐hoc analysis, lusutrombopag was superior to placebo as treatment for managing thrombocytopenia in patients with hepatocellular carcinoma undergoing planned invasive procedures. Over two thirds of patients receiving lusutrombopag avoided having platelet transfusions with their procedure. The efficacy of lusutrombopag in patients with hepatocellular carcinoma was consistent with that of patients with other chronic liver disease diagnoses.image