Three criteria for radiological response on survival in patients with hepatocellular carcinoma treated with lenvatinib

Abstract

Lenvatinib (LEN) is a newly approved, multikinase inhibitor for treating unresectable hepatocellular carcinoma. In the present study, we investigated the impact of three different criteria for evaluating radiological objective response (OR) on overall survival in real-world data.Methods: Consent for LEN therapy was obtained from 51 patients from April 2018 to March 2019. A total of 40 patients who received a minimal cumulative duration of 4 weeks of LEN were included in the analysis. Enhanced computed tomography scan was performed at baseline and every 4-8 weeks after LEN administration. Overall survival and OR were assessed with three different evaluations, as follows: Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria. Results:The average observation period for all participants after LEN introduction was 209.4 ± 77.5 days. The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria identified 10 of 40 (25.0%), 15 of 40 (37.5%), and 18of 40 (45.0%) patients with OR, respectively. The median overall survival in progressive disease evaluated by each criterion was 227 days. This result was significantly shorter than OR. Furthermore, the cumulative duration of LEN administration (>150 days) represented a significant prognostic factor (HR 0.160. 95% CI 0.039-0.646, P = 0.001). Conclusion:The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria were useful therapeutic evaluation methods in LEN therapy for unresectable hepatocellular carcinoma. LEN's appropriate effect evaluation and management might lead to a better prognosis.

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. 4,[14][15][16][17][22][23][24][25][26] 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. Hiraoka et al reported that appetite loss was an important AE in lenvatinib treatment for discontinuation clinically.…”

“…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.…”

Analyses of objective response rate, progression‐free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study

“…To date, lenvatinib showed a higher ORR of 41.3% compared with sorafenib in a randomized phase II non‐inferiority trial, and it also showed the ORR of 37.5–40.7% assessed by modified Response Evaluation Criteria in Solid Tumors in clinical settings . Meanwhile, a relative higher ORR of 61.3% was reported in patients with intermediate‐stage HCC according to the Japanese subgroup analysis of a randomized phase III study .…”

“…To date, lenvatinib showed a higher ORR of 41.3% compared with sorafenib in a randomized phase II noninferiority trial, 5 and it also showed the ORR of 37.5-40.7% assessed by modified Response Evaluation Criteria in Solid Tumors in clinical settings. [25][26][27][28] Meanwhile, a relative higher ORR of 61.3% was reported in patients with intermediate-stage HCC according to the Japanese subgroup analysis of a randomized phase III study. 29 However, Ueshima et al reported that patients with Child-Pugh score 5 and ALBI grade 1 showed better tolerability and it was easier to maintain the initial dose of lenvatinib than those with poor hepatic function, insisting that ALBI grade 1 was the favorable factor affecting the ORR in the multivariate analysis.…”

Relative dose intensity over the first four weeks of lenvatinib therapy is a factor of favorable response and overall survival in patients with unresectable hepatocellular carcinoma

“…Starting with a reduced dose was permitted based on the patient's condition and the preference of the attending physicians. Tumor assessment was done in accordance with the modified Response Evaluation Criteria in Solid Tumor (mRECIST), using dynamic CT within 4-8 weeks and every 8 weeks thereafter [16,17]. During follow up, all patients were measured routine blood-chemistry and tumor markers testing every 2-4 weeks.…”