Abstract
Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP≥400ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75years). Individual patient data were pooled from REACH (baseline AFP ≥400ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). A total of 542 patients (<65years: n=302; ≥65 to <75years: n=160; ≥75years: n=80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65years subgroup. Ramucirumab prolonged OS in patients <65years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75years (0.602; 0.419-0.866) and ≥75years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75years.
Highlights
Hepatocellular carcinoma (HCC) is a relatively common cancer associated with significant morbidity and mortality.[1,2,3] In eastern Asia and Africa, hepatocellular carcinoma (HCC) usually presents in younger patients, whereas in Japan and Western countries, HCC generally presents at an older age
MTKIs like lenvatinib and regorafenib have shown similar efficacy outcomes, and cabozantinib has shown similar efficacy and safety profiles[18] between patients with HCC aged
These results suggest that ramucirumab can be used in patients with HCC irrespective of age, including elderly patients ≥75 years of age
Summary
Hepatocellular carcinoma (HCC) is a relatively common cancer associated with significant morbidity and mortality.[1,2,3] In eastern Asia and Africa, HCC usually presents in younger patients, whereas in Japan and Western countries, HCC generally presents at an older age. Ramucirumab, a human immunoglobulin G1 monoclonal antibody that inhibits ligand activation of vascular endothelial growth factor receptor 2 (VEGFR2), was assessed for efficacy and safety vs placebo in patients with HCC after prior sorafenib in two global, randomized, double-blind, placebo-controlled phase III clinical trials (REACH and REACH-2).[14,15] A prespecified subgroup analysis of patients with HCC with baseline alpha-fetoprotein (AFP) levels ≥400 ng/mL in REACH showed a significant overall survival (OS) benefit in this subgroup (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.51-0.90)[15]; this was confirmed in the REACH-2 trial (HR, 0.710; 95% CI, 0.531-0.949; P = .0199), without compromising patient-reported disease symptoms as assessed by the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptoms Index (FHSI)-8.14 Ramucirumab had an acceptable safety profile in these trials and may be considered for HCC treatment in elderly patients This post-hoc analysis evaluated the efficacy, safety and patient-reported outcomes (PROs) for ramucirumab in three prespecified age subgroups (
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