Up-titration of sorafenib for hepatocellular carcinoma: Impact on duration of exposure and cost.

Abstract

385 Background: Few data exist how sorafenib starting dose impacts duration of exposure and cost of sorafenib therapy for patients with HCC. Methods: HCC patients exposed to sorafenib, initial doses, number of sorafenib fills, and medication exposure days were identified from the VA CDW using ICD9 codes and pharmacy records. ICD9 codes, CPT codes, AUDIT-C surveys and laboratory tests were utilized to characterize underlying liver disease, calculate Child-Turcotte-Pugh (CTP) and MELD scores. Two abstractors achieved 100% chart verification of tumor number, size, MVI/EHS on imaging proximate to sorafenib to quantify Barcelona Clinic Liver Cancer (BCLC) stage and to determine the provider specialty initiating sorafenib. Results: 2292 patients with BCLC B-C HCC, CTP A cirrhosis with ECOG PS ≤ 2 prescribed sorafenib for HCC between 2007 and 2015 were included in this interim analysis. Median age was 62; 98.8% were male, 61.8% white/26.0% black; Pre-sorafenib BCLC B-43%/C-57%. Prescription at full-dose became less common over 2007-2015, dropping from 80% to 48%. First-dose up-titration was more commonly done by hepatologists (21% vs. 4.5%, p < 0.0001), but oncologists were more likely to up-titrate at the second prescription (8.9% vs. 3.8%, p < 0.001). Overall, 38% of first sorafenib prescriptions were initiated at doses below 800mg/day; 43% were up-titrated whereas 57% never up-titrated. Patients starting at < 800 mg/d received fewer total pills (median 284 vs. 360, p = 0.008) but a greater number of prescription fills (median 4 vs. 3, p < 0.0001) and longer exposure duration (median 120 vs 90 days, p = 0.0012) at lower total cost (median $8,143 vs $9,685, p < 0.0001). Median overall survival for those starting < 800mg/d was not significantly different from full dose initiators (median 284 vs. 292 days, p = 0.33). Conclusions: Initiation of sorafenib < 800mg/d was associated with lower pill utilization, but longer exposure duration and equivalent survival at lower cost. Starting at a lower dose with uptitration may select patients with a higher likelihood of sustained benefit and improve cost-effective utilization of resources. This approach should be tested prospectively.