Clinical Effect of Lenvatinib Re-Administration after Transcatheter Arterial Chemoembolization in Patients with Intermediate Stage Hepatocellular Carcinoma

Abstract

The present study clarified the prognosis of intermediate-stage hepatocellular carcinoma (HCC) patients who received lenvatinib (LEN) followed by transcatheter arterial chemoembolization (TACE) on demand. We retrospectively evaluated 88 intermediate-stage HCC patients who received LEN. The median age was 74 (range: 47-92) years old, 67 patients were male, and 82 were classified as Child-Pugh A. LEN was administered until disease progression or discontinuation due to adverse events (AEs). The mean duration of LEN treatment was 7.0 months. The response and disease control rates were 51.1% and 89.8%, respectively. The median progression-free survival and overall survival (OS) after the initiation of LEN were 6.8 months and 29.9 months, respectively. The OS in patients for whom LEN was re-administered after TACE (TACE-LEN) was better than that in patients who received other therapies (e.g., only TACE, TACE-other therapy, or only other therapy) even with propensity score matching (p = 0.008). A Cox proportional hazard analysis showed that TACE-LEN was most strongly associated with the OS (hazard ratio: 0.083, 95% confidence interval: 0.019-0.362, p = 0.001). LEN was administered for approximately 11.1 months after TACE. In intermediate-stage HCC patients who can tolerate LEN without discontinuation due to AEs, TACE-LEN may prolong the prognosis.

Keywords: TACE; hepatocellular carcinoma (HCC); intermediate stage; lenvatinib; on demand.

Figure 1

Kaplan–Meier curve of progression-free survival and overall survival in all patients. (a) Progression-free survival (PFS). The median PFS was 6.8 months. (b) Overall survival (OS). The median OS was 29.9 months.

Figure 2

Kaplan–Meier curve of the overall survival and progression-free survival according to post-treatment in cases in which lenvatinib therapy was discontinued. Cases in which lenvatinib (LEN) was discontinued were divided into six groups. A: TACE-LEN, LEN was re-administered after TACE. B: TACE-other therapy, sorafenib, regorafenib, ramucirumab, cabozantinib, and atezolizumab + bevacizumab were introduced after TACE. C: Only TACE. D: Other therapy, only drug therapy without TACE. E: RFA or resection. F: No therapy. (a) OS from the initiation of LEN. The OS in group A was significantly better than that in groups B, C, D, or F. (b) The PFS from the first initiation of LEN. There was no significant difference between group A and groups B, C, D, or F. (c) OS from the first discontinuation of LEN in patients for whom LEN was administered in the first line and who underwent post-treatment. The OS in group A was significantly better than that in groups B, C, or D. (d) The PFS from the second initiation of LEN. LEN, lenvatinib; TACE, transcatheter arterial chemoembolization; OS, overall survival; PFS, progression-free survival.

Figure 2

Kaplan–Meier curve of the overall survival and progression-free survival according to post-treatment in cases in which lenvatinib therapy was discontinued. Cases in which lenvatinib (LEN) was discontinued were divided into six groups. A: TACE-LEN, LEN was re-administered after TACE. B: TACE-other therapy, sorafenib, regorafenib, ramucirumab, cabozantinib, and atezolizumab + bevacizumab were introduced after TACE. C: Only TACE. D: Other therapy, only drug therapy without TACE. E: RFA or resection. F: No therapy. (a) OS from the initiation of LEN. The OS in group A was significantly better than that in groups B, C, D, or F. (b) The PFS from the first initiation of LEN. There was no significant difference between group A and groups B, C, D, or F. (c) OS from the first discontinuation of LEN in patients for whom LEN was administered in the first line and who underwent post-treatment. The OS in group A was significantly better than that in groups B, C, or D. (d) The PFS from the second initiation of LEN. LEN, lenvatinib; TACE, transcatheter arterial chemoembolization; OS, overall survival; PFS, progression-free survival.

Figure 3

Kaplan–Meier curve for OS after adjustment by propensity score matching in patients who received LEN in the first line. TACE-LEN: LEN was re-administered after TACE. (a) OS from the initiation of LEN. (b) OS from the first discontinuation. The OS in the TACE-LEN group was significantly prolonged in comparison to patients who received other therapies. LEN, lenvatinib; TACE, transcatheter arterial chemoembolization; OS, overall survival.