Efficacy and Safety of Ramucirumab in Patients with Unresectable Hepatocellular Carcinoma with Progression after Treatment with Lenvatinib

Abstract

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment. Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure. Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline. Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.

Comparison of the Clinical Outcome of Ramucirumab for Unresectable Hepatocellular Carcinoma with That of Prior Tyrosine Kinase Inhibitor Therapy

“…The change in the AFP value after the start of ramucirumab was compared with the best response by mRECIST. It has already been reported that AFP reduction after TKIs, such as sorafenib and lenvatinib, may be useful for predicting treatment response [10-12], and similarly, Kasuya et al [13] reported that the rate of change in AFP may help predict efficacy even with ramucirumab. In the present study, disease control was obtained in 5 of 6 cases in which AFP decreased in the 1st month after the start of ramucirumab, whereas disease control was not obtained in 5 of 6 cases in which AFP continued to increase.…”

“…Kuzuya et al [14] reported that the DCR was 80.0%, and the median time to progression (TTP) was 3.1 months. In addition, Kasuya et al [13] reported that the DCR was 28.6%, and median PFS was 41 days, and Hiraoka et al [15] reported that the DCR was 42.3% and the median TTP was 2.0 months.…”

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

“…A retrospective study reported a disease control rate (DCR) of 60% in 10 patients who received ramucirumab treatment after lenvatinib [86]. Another retrospective study showed a DCR of 33% in six patients that were treated with ramucirumab after lenvatinib [87]. The populations of these two studies were too small to draw any definitive conclusions regarding the efficacy of ramucirumab treatment after lenvatinib failure.…”

Clinical Evaluation of Ramucirumab for the Treatment of Hepatocellular Carcinoma (HCC): Place in Therapy

“… 26 In a smaller study, 7 patients with unresectable HCC and AFP ≥ 400 ng/mL and previously treated with lenvatinib, received ramucirumab and achieved a DCR of 28.6% and a mPFS of 41 days. 27 A recent similar study with a larger sample size (n = 28) reported a DCR of 42.3% and a mPFS of 2.0 months following failure of lenvatinib. 28 In a study by Hatanaka et al exploring the role of albumin-bilirubin score in predicting outcome of ramucirumab for treatment of patients with advanced HCC, the treatment response of 16 patients was reported: 29 DCR ranged between 28.6% and 100%, mOS ranged between 3.0 months and 6.7 months, and mPFS ranged between 1.4 and 7.5 months (depending on albumin-bilirubin score).…”