Hepatocellular Carcinoma In Phase Research Articles

Impact of Hepatitis Virus on the Feasibility and Efficacy of Anticancer Agents in Patients With Hepatocellular Carcinoma in Phase I Clinical Trials.

Chronic viral hepatitis is a risk factor for liver fibrosis and hepatocellular carcinoma (HCC). Patients with advanced HCC have limited effective therapeutic options and are considered potential candidates for early phase clinical trials of anti-cancer agents. The impact of chronic viral hepatitis on the efficacy of anticancer agents for patients with HCC in phase I trials (P-Is) still remains unclear and has not been reported. We retrospectively analyzed the outcomes of consecutive HCC patients in P-Is conducted in a single institute, focusing on chronic viral hepatitis. Of 85 patients enrolled in P-Is, 46 (54%) patients positive and 39 (46%) patients negative for chronic viral hepatitis showed no significant difference in clinical and laboratory variables and on the point of the best response based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria; moreover, the frequency of Grade ≥3 adverse events (AE) was not significantly different. The median time to treatment failure (TTF) and overall survival (OS) from the P-I enrolment were 2.0 and 13.7 months, respectively. No patient experienced reactivation of hepatitis B virus (HBV) or treatment-related death. Chronic viral hepatitis does not independently affect the outcomes of anticancer drugs. Advanced HCC patients with chronic viral hepatitis could be feasible for P-Is.

53P - Impact of chronic hepatitis virus infection on the feasibility and efficacy for Asian patients with hepatocellular carcinoma in phase I clinical trials

Background: In Asia, chronic hepatitis B and C virus infections (CHVI) are major risk factors for liver fibrosis and hepatocellular carcinoma (HCC). Patients with advanced HCC have limited effective therapeutic options and are potential candidates for early phase clinical trials for new anti-cancer agents. The impact of CHVI on the feasibility and efficacy for patients with HCC in Phase I trials (P-Is) has not been reported or elucidated in Western countries. Methods: We retrospectively analyzed the characteristics and outcomes of HCC patients participating in P-Is, with emphasis on CHVI. Patients testing positive for anti-hepatitis C virus (HCV) antibody or hepatitis B virus surface antigen (HBsAg) were diagnosed with CHVI. Results: Eighty-five patients were enrolled in P-Is at our center. There were no significant differences in the clinical and laboratory variables, including the liver function test results, between the 46 (54%) CHVI-positive and 39 (46%) CHVI-negative patients in this study. The median time to treatment failure (TTF) and overall survivals (OS) from enrollment of the P-I were 60 days (95% confidence interval [CI]: 51–85) and 412 days (95% CI: 267–478), respectively. There is no significant difference between positive and negative for hepatitis virus in the best response based on the RECIST. The frequency of abnormal liver function test (LFT) adverse events (grade ≥ 3) was significantly different among CHVI-positive and -negative patients. No patient discontinued P-I treatment secondary to abnormal LFT results or developed reactivation of hepatitis virus, and no treatment-related mortality was observed. Multivariate analysis revealed that the number of prior systemic treatments significantly contributed to poor TTF (≥2; HR: 2.1, 95% CI: 1.3–3.6, P = 0.004) and that poor Eastern Cooperative Oncology Group Performance Status significantly contributed to poor OS (≥1; HR: 1.9, 95% CI: 1.0–3.4, P = 0.04). Conclusions: CHVI did not independently predict TTF and OS. Abnormal LFT adverse events could be related to CHVI but did not lead to discontinuation of P-I treatment. Thus, patients advanced HCC with CHVI can be enrolled in the P-Is. Legal entity responsible for the study: N/A Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.