Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Prognosis, efficacy, and safety by liver disease etiology

Background

REACH was a global, randomized, phase 3 study evaluating the efficacy and safety of single-agent RAM in pts with advanced HCC after prior sorafenib. While a significant median overall survival (OS) benefit was not observed in the ITT population (N = 565), a survival benefit was observed in pts with a baseline alpha-fetoprotein (AFP) ≥400 ng/mL (n = 250), OS 7.8 mo RAM vs 4.2 mo placebo [PBO], HR 0.67; P= .006). Ad hoc retrospective analyses on the survival and safety of pts by liver disease etiology were performed.

Methods

In each disease etiology subgroup (Hepatitis B [HepB], HepC, or Other) per case report form, OS was estimated using Kaplan-Meier analysis and compared by log-rank test and Cox proportional hazards model. The objective response rate (ORR) was defined as the proportion of pts with best overall response of CR or PR.

Results

Baseline pt characteristics were generally balanced between treatment arms in each subgroup. 37% were reported as HepB (n = 209), 27% HepC (n = 154), and 36% Other (n = 202). HepB pts were more likely to be Asian, ECOG PS 1, have extra-hepatic spread, and AFP ≥400ng/mL. The OS for RAM compared to PBO was 8.2 vs 5.4 mo in HepB (HR 0.79; P= .11); 9.2 vs 8.8 mo in HepC (HR 0.95; P = .79); and 11.1 vs 8.5 mo in Other pts (HR 0.85; P= .33). ORR was 2.8% RAM vs 0% PBO in HepB pts, 10.3% vs 2.6% in HepC pts, and 9.1% vs 0% in Other pts. In pts with baseline AFP ≥400 ng/mL, the OS for RAM compared to PBO was 6.6 vs 4.0 mo in HepB (HR 0.67; P= .04); 8.2 vs 4.8 mo in HepC (HR 0.89; P= .68); and 8.5 vs 4.3 mo in Other pts (HR 0.45; P= .003). In all subgroups with baseline AFP

Conclusions

HepB pts had shorter survival compared to pts with HepC or Other. In all etiology subgroups with a baseline AFP ≥400 ng/mL, a potential improvement in survival with RAM was observed. RAM was well tolerated with a similar safety profile in all etiology subgroups.

Clinical trial identification

NCT01140347

Legal entity responsible for the study

Eli Lilly and Company

Funding

Eli Lilly and Company

Disclosure

T. Okusaka: Honoraria, Consulting/Advisory roles: Eli Lilly, BMS, Merck, Blueprint, Eisai, Biocompatibles, Guerbert, Roche, Bayer, Genentech, Boehringer-Ingelheim, GSK, Celsion, Novartis. Research funding: Eli Lilly, Bayer, Novartis, Boehringer-Ingelheim. J.-F. Blanc: Advisory Board: Lilly Oncology, Bayer SP.

I. Chau: Honoraria: Taiho, Pfizer, Amgen, Eli-Lilly, Bayer. Advisory role: Sanofi Oncology, Eli-Lilly, Bristol Meyers Squibb, Merck Serono, MSD, Gilead Science. Research funding: Janssen-Cilag, Sanofi Oncology, Roche, Merck-Serono. L. Yang, P. Abada: Employee and stock owner of Eli Lilly and Company. A.X. Zhu: Funding: Eli Lilly and Company.