In the whole population, the dose-adjusted strategy was more cost-effective than the full dose in terms of both LYG and QALY. Specifically, compared with BSC the full-dose strategy had an ICER of €63,197 for LYG and of €69,344 for QALY, while dose-adjusted strategy had an ICER of €25,874 for LYG and of €34,534 for QALY. As in the entire SOFIA cohort, in the BCLC B patients the dose-adjusted strategy was more cost-effective than the full dose in terms of both LYG and QALY. Specifically, compared with BSC the full-dose

strategy had an ICER of €44,794 for LYG and of €57,385 for QALY, while the dose-adjusted strategy had an learn more ICER of €41,782 for LYG and of €54,881 for QALY. Similarly, in BCLC C patients, considering both LYG and QALY, the dose-adjusted strategy was more cost-effective than the full dose. Specifically, compared with BSC the full-dose strategy had an ICER of €59,922 for LYG and of €65,551 for QALY, while the dose-adjusted strategy had an ICER of €20,896 for LYG and of €27,916 for QALY. Performing analysis in the subgroup of the SOFIA cohort obtained after excluding patients with early radiologic progression, ICER per QALY in dose-adjusted sorafenib strategies

marginally improved. Specifically in this subgroup of patients, dose-adjusted sorafenib strategy had an ICER per QALY of €25,569 for BCLC C and of €58,265 for BCLC B patients. One-way 17-DMAG (Alvespimycin) HCl sensitivity analysis was done FK228 molecular weight for two dominant strategies: dose-adjusted sorafenib therapy for both BCLC B and C HCC patients. Figure 3 summarizes the results of one-way sensitivity analyses, using tornado diagrams. Analyses showed that the results of the model were most sensitive to an assumption on survival rates of BSC patients, sorafenib treatment duration, and type of survival distribution. Changes in survival rates in patients managed with BSC had a great effect on cost-effectiveness. In fact, sensitivity

analysis with a hypothesized variation of survival of ±30% in BSC patients showed that ICER for QALY ranged significantly from €41,325 to €100,544 in BCLC B (Fig. 3A) and from €24,450 to €36,032 in BCLC C (Fig. 3B) patients treated with dose-adjusted sorafenib. The cost effectiveness of dose-adjusted sorafenib was sensitive to change (±30%) in the treatment duration. With a longer time of therapy, the ICER for QALY impairs both the BCLC B and BCLC C patients. Instead, for the sensitivity analysis on the disease costs, a variation of ±30% was assessed, and the model had low sensitivity. With an increase in the disease costs, the ICER for LYG and for QALY marginally increased in both BCLC B (Fig. 3A) and BCLC C (Fig. 3B) dose-adjusted strategies. Lower variations were found for both strategies by applying a discount rate ranging from 0% to 5%.