Factors Contributing to the Prognosis after Second-line Therapy with Ramucirumab in Advanced Hepatocellular Carcinoma

Abstract

Objective Multiple therapeutic agents exist for advanced hepatocellular carcinoma (HCC), but prognostic factors in second-line and subsequent therapies are unclear. Ramucirumab is a molecular-targeted agent effective against hepatocytes with alpha-fetoprotein (AFP) >400 ng/mL after sorafenib failure. We examined the prognostic factors and efficacy of ramucirumab with prior therapy other than sorafenib. Methods In our retrospective multicenter study, 33 patients were treated with ramucirumab for HCC with prior therapy other than sorafenib, including 1 patient who received 2 lines of ramucirumab. We analyzed background factors, liver reserve, the prognosis, and treatment duration and efficacy. ResultsThe median albumin-bilirubin (ALBI) value showed little change during ramucirumab treatment. The ALBI value improved in 32% of patients, and their prognoses were better than in those who did not improve. Response and efficacy rates were not as high as those in the REACH-2 study but were similar when limited to patients with 2,500 ng/mL AFP. Thirteen patients received further treatment after ramucirumab failure and they had a significantly better prognosis from ramucirumab administration and also had a significantly better prognosis from the start of the first tyrosine kinase inhibitor than who did not received further treatment. In univariate and multivariate analyses of prognostic factors, the continuation of treatment with another drug after ramucirumab failure and a good ALBI value at initiation were significant. The presence of a ramucirumab response and treatment duration were not associated with the prognosis. A good ALBI value at initiation and ALBI value improvement during treatment were also identified as independent factors associated with eligibility for further treatment after ramucirumab failure. The treatment line did not correlate with the availability of treatment with another drug after treatment failure. Conclusions ALBI value improvement with ramucirumab treatment allows for subsequent treatment after failure and an improved overall prognosis.

Impact of post‐progression survival in second‐line treatment with molecular target agents for unresectable hepatocellular carcinoma

“…A search of the PubMed database identified 24 cohorts in 23 studies encompassing 2074 patients treated with REG (Figure 1 and Table ) 11,14–35 . Similarly, six cohorts from six studies comprising 621 patients treated with RAM 12,36–40 were identified, as well as seven cohorts from six studies involving 1240 patients treated with CAB 13,23,33,41–43 (Figure 1 and Tables and , respectively). In the present study, patients with Child‐Pugh B were identified with 183/1622 (11.3%), 53/621 (8.5%), and 37/909 (9.2%) in REG, RAM, and CAB cohort, respectively (Tables ).…”

“…Liver function has been shown to be preserved during RAM treatment. 38,39 It might be helpful for clinicians to introduce further later-line treatments. Implementing sequential therapies in patients with preserved liver function and good general health condition can effectively prolong OS by suppressing tumor progression, making it a critical consideration in the management of unresectable HCC.…”

“…In the present study, minimal correlation between PFS and OS was found but a strong correlation between PPS and OS was found in RAM. Liver function has been shown to be preserved during RAM treatment 38,39 . It might be helpful for clinicians to introduce further later‐line treatments.…”