Correlation between Early Tumor Marker Response and Imaging Response in Patients with Advanced Hepatocellular Carcinoma Treated with Lenvatinib

Abstract

<b><i>Aim:</i></b> This study investigated early tumor marker response and treatment response in patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib. <b><i>Methods:</i></b> Twenty patients with advanced HCC who received lenvatinib were enrolled in this retrospective study. α-Fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP) levels were measured before treatment as well as 2 and 4 weeks after treatment. The objective response rate was evaluated by mRECIST at 6 weeks. <b><i>Results:</i></b> The response rate was 30% (complete response/partial response/stable disease/progressive disease: <i>n</i> = 0/6/6/8 cases) by mRECIST. At 4 weeks, the AFP levels of 12 patients (80%) were lower than at baseline. The AFP levels of 9 patients (60%) continued decreasing from 2 weeks to 4 weeks (sustained-reduction group). In this group, the response rate was 67%. The median AFP change rate was –39% at 4 weeks. In imaging responders, the AFP change rate significantly decreased (<i>p</i> = 0.02). The DCP change rate had no significant correlation with imaging response. The AFP-sustained-reduction group had significantly higher adherence to lenvatinib than the non-sustained-reduction group (<i>p</i> = 0.02). <b><i>Conclusion:</i></b> With lenvatinib therapy for HCC, the AFP levels of most patients had declined at 2 weeks, and at 4 weeks the AFP-sustained-reduction group demonstrated a higher objective response.

Favorable radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma

“…Physicians sometimes reduce lenvatinib doses due to lenvatinib‐related AEs . In the present study, the most frequent cause that led to dose reduction or discontinuation of lenvatinib within 6 weeks was appetite loss (72.5%), and the median 2–6 W‐RDI (69.6%) was significantly lower than the median 0–2 W‐RDI (100%) due to the dose reduction or temporary interruption of lenvatinib.…”

“…There have been several reports on the evaluation of antitumor response to lenvatinib using initial imaging, which were assessed from 4 to 8 weeks after lenvatinib introduction, in clinical practice. [14][15][16][17][22][23][24][25][26] These reports showed ORRs of 29.4-45.0% and DCRs of 60.0-93.0%. Similarly, the present study showed that relative to the image at baseline, the 6 W-ORR and 6 W-DCR were 50.0% and 90.0%, respectively.…”

“…There have been several reports on the evaluation of antitumor response to lenvatinib using initial imaging, which were assessed from 4 to 8 weeks after lenvatinib introduction, in clinical practice . These reports showed ORRs of 29.4–45.0% and DCRs of 60.0–93.0%.…”

“…There have been a few reports on the early AFP response in patients treated with lenvatinib in the clinical setting . Kodama et al .…”

“…There have been a few reports on the early AFP response in patients treated with lenvatinib in the clinical setting. 15,24 Kodama et al reported that the proportion of patients who had a decrease in AFP from baseline to 2 and 4 weeks was 87% and 80%, respectively, with a median rate of AFP change of À29% (À84 to 34%) at 2 weeks, and À39% (À94 to 2145%) at 4 weeks; furthermore, the ORR by mRECIST at 6 weeks was high (67%) in patients whose AFP levels continued to decrease from 0, 2, to 4 weeks. 24 In the present study, the median AFP ratio at 2 weeks was 0.6 (range 0.3-1.3), and the AFP ratio at 2 weeks was a significant factor associated with PR of 2 W-response.…”