Unfortunately, as yet, translating promising preclinical data into significant clinical benefits for HCC patients has been disappointing across multiple drugs, drug combinations, and trial designs [62C64, 70, 71]

Unfortunately, as yet, translating promising preclinical data into significant clinical benefits for HCC patients has been disappointing across multiple drugs, drug combinations, and trial designs [62C64, 70, 71]. median OS was 8.55 months (95% CI: 7.00C13.9) for patients treated with B+E and 8.55 months (95% CI: 5.69C12.2) for patients receiving S. The hazard ratio (HR) for OS was 0.92 (95% CI: 0.57C1.47). The median EFS was 4.37 months (95% CI: 2.99C7.36) for patients receiving B+E and 2.76 months (95% CI: 1.84C4.80) for patients receiving S. The HR for EFS was 0.67 (95% CI: 0.42C1.07; = 0.09), favoring B+E over S. When OS was assessed among patients who were Child-Pugh class A, the median OS was ENPP3 11.4 months (95% CI: 7.5C15.7) for patients treated with B+E (= 39) and 10.26 months (95% CI: 5.9C13.0) for patients treated with S (= 38) ZK824859 (HR = 0.88; 95% CI: 0.53C1.46). Conclusions: There was no difference in efficacy between the B+E and S arms, although the safety and tolerability profile tended to favor B+E over S based on competing risk analysis. Clinical trial No. “type”:”clinical-trial”,”attrs”:”text”:”NCT00881751″,”term_id”:”NCT00881751″NCT00881751. tests; comparisons of categorical variables were made with Fishers exact test. RRs and toxicity rates were estimated with exact 95% CIs. A competing risks approach was used to analyze time to progression, where deaths from non-HCC causes and discontinuation due to adverse events (AEs) were considered competing risks. Specifically, patients were (a) censored if they neither had died nor had disease progression by the end of the study; (b) treated as having progression if they had disease progression prior to death or the end of the study, or if death was due to disease; (c) treated as having died from other cause if they had died from a cause unrelated to the disease and prior to another event; and (d) treated as having discontinued treatment due to an AE if they were removed from the study due to a study-related AE. Cumulative incidence [60] was calculated for each class of event and graphically displayed. Cumulative risk regression [61] was used ZK824859 to calculate HRs comparing risk rates and their 95% CIs. Wald tests were used for testing the significance of the HRs. Results Patients A total of 95 patients were registered and randomized, 5 patients withdrew, and 90 patients received at least 1 dose of the study drug and were evaluable (Fig. 1). The patient characteristics are summarized in Table 2. Open in a separate window Fig. ZK824859 1. Enrollment summary. Table 2. Distribution of clinical and demographic characteristics of the patients (= 90) = 43)= 47)value1(%) unless specified otherwise. S, sorafenib; B+E, bevacizumab plus erlotinib. 1values based on two-sample test for continuous variables; Fishers exact test for categorical variables. Efficacy The efficacy results are summarized in Table 3 and Figure 2. Investigator assessment, confirmed by the diagnostic imaging collaborator at each institution and by centralized blinded radiology review, was used in determining tumor response and progression. The median OS of the patients treated with B+E and those treated with S were essentially the same. The 12-month survival was 37% (95% CI: 25C55) among patients treated with B+E, and 35% (95% CI: 22C55) among patients treated with S. The HR for OS was 0.92 (95% CI: 0.57C1.47). The objective RR for B+E was 15% (95% CI: 6.2C28) and that for S was 9% (95% CI: 2.6C22). OS did not differ between the B+E and the S arm based on ECOG PS or BCLC stage A or B versus BCLC stage C. Open in a separate window Fig. 2. Survival summary. a Overall survival. b Overall survival by ECOG status. c Overall survival by BCLC stage. d Overall survival Child-Pugh class A versus B. e Event-free survival. f Event-free survival by BCLC stage. The value for testing overall survival was 0.73 using the Cox proportional hazards model; however, a hypothesis test for overall survival comparing the two groups was not included in the study design due to insufficient power. Bev, bevacizumab. Table 3. Efficacy summary = 38; B+E, = 39)= 43)9 (2.6C22)8.6 (5.7C12.2)35 (22C55)2.76 (1.84C4.80)10.26 (5.9C13.0)40 (26C61)B+E= 47)15 (6.2C28)8.6 (7.0C13.9)37 (25C55)4.37 (2.99C7.36)11.4 (7.5C15.7)45 (31C65) Open in a separate window Values in parentheses are 95% CI. mOS, median overall survival; mEFS, median event-free survival; S, sorafenib; B+E, bevacizumab plus erlotinib. Since most other randomized HCC trials included only patients with Child-Pugh class A liver function [5, 62C65], OS was also assessed for the subgroup of patients in this ZK824859 study who were Child-Pugh class A versus ZK824859 B7 (Fig. 2d). The median OS of the patients treated with B+E (= 39) was 11.4 months (95% CI: 7.5C15.7) and that of the patients treated with S (= 38) was 10.26 months (95% CI: 5.9C13.0) (median OS in the SHARP trial: 10.7 months). The 12-month survival among the Child-Pugh class A patients was 45% (95% CI: 31C65) with B+E and.