Impact of baseline hepatitis B viremia and management on outcomes in patients (Pts) with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP): Outcomes from REACH-2.

569 Background: REACH (NCT01140347) and REACH-2 (NCT02435433) were global, randomized, blinded, placebo (PL)-controlled phase 3 trials of ramucirumab (RAM) in pts with advanced HCC following sorafenib. REACH-2 limited enrollment to pts with AFP ≥400 ng/mL, and met its primary OS endpoint, consistent with the prespecified REACH subgroup with baseline AFP ≥400 ng/mL. Analysis of pooled individual pt data from REACH (AFP ≥400 ng/mL) and REACH-2 showed improved OS with RAM vs PL for pts with hepatitis B virus (HBV) etiology (7.7 vs 4.5 mos; HR 0.74, 95% CI 0.55, 0.99). Here we investigate survival and liver function in REACH-2 pts with HBV etiology tested for serum HBV DNA. Methods: Pts had advanced HCC, Child-Pugh A, ECOG PS 0/1, AFP ≥400 ng/mL, prior sorafenib treatment, and were randomized (2:1) to receive RAM 8 mg/kg or PL Q2W. Pretreatment serum HBV DNA was quantified by HBV-specific PCR (Roche) by a central lab. HBV DNA > 15 IU/mL were detectable (HBV DNA+), < 15 IU/mL were undetectable (HBV DNA-). OS in pooled treatment arms was evaluated using Kaplan-Meier method and Cox proportional hazards model. Liver function was assessed at baseline and before each cycle with the ALBI linear predictor. Outcomes were assessed by concomitant antiviral therapy. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Results: Of 107 REACH-2 pts with HBV etiology, 106 had available PCR samples and were included in a pooled analysis (70 RAM and 36 PL pts). 48 pts were HBV DNA+ and 58 pts were HBV DNA-. HBV DNA+ pts had poorer median OS vs HBV DNA- pts (5.3 vs 10.1 mos, unstratified HR 1.45 95% CI 0.93, 2.28). HBV DNA+ pts taking concomitant antiviral therapy (n = 36) had numerically improved OS compared with those without (n = 12) (5.8 vs 4.0 mos). No difference in OS was noted for HBV DNA- pts by antiviral therapy use (n = 39 antiviral; n = 19 no antiviral) (10.2 vs 9.7 mos for yes vs no antiviral). In pts taking antiviral therapy, regardless of HBV DNA serology, liver function was improved and liver injury/failure related AEs were less frequent. Conclusions: Our data reinforce the use of antiviral therapy to improve outcomes in pts with advanced HBV-associated HCC and elevated AFP. Clinical trial information: NCT02435433.