Lenvatinib-Transarterial Chemoembolization Sequential Therapy as an Effective Treatment at Progression during Lenvatinib Therapy for Advanced Hepatocellular Carcinoma

Yusuke Kawamura; Masahiro Kobayashi; Junichi Shindoh; Yuta Kobayashi; Satoshi Okubo; Licht Tominaga; Akira Kajiwara; Kayoko Kasuya; Soichi Iritani; Shunichiro Fujiyama; Tetsuya Hosaka; Satoshi Saitoh; Hitomi Sezaki; Norio Akuta; Fumitaka Suzuki; Yoshiyuki Suzuki; Kenji Ikeda; Yasuji Arase; Masaji Hashimoto; Tokuyo Kozuka; Hiromitsu Kumada

doi:10.1159/000510299

Lenvatinib-Transarterial Chemoembolization Sequential Therapy as an Effective Treatment at Progression during Lenvatinib Therapy for Advanced Hepatocellular Carcinoma

Liver Cancer. 2020 Dec;9(6):756-770. doi: 10.1159/000510299. Epub 2020 Oct 30.

Authors

Yusuke Kawamura^{1

2}, Masahiro Kobayashi^{1

2}, Junichi Shindoh^{2

3}, Yuta Kobayashi^{2

3}, Satoshi Okubo^{2

3}, Licht Tominaga^{2

4}, Akira Kajiwara^{1

2}, Kayoko Kasuya^{1

2}, Soichi Iritani^{1

2}, Shunichiro Fujiyama^{1

2}, Tetsuya Hosaka^{1

2}, Satoshi Saitoh^{1

2}, Hitomi Sezaki^{1

2}, Norio Akuta^{1

2}, Fumitaka Suzuki^{1

2}, Yoshiyuki Suzuki^{1

2}, Kenji Ikeda^{1

2}, Yasuji Arase^{1

2}, Masaji Hashimoto^{2

3}, Tokuyo Kozuka^{2

4}, Hiromitsu Kumada^{1

2}

Affiliations

¹ Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
² Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
³ Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.
⁴ Radiation Oncology Division, Department of Radiology, Toranomon Hospital, Tokyo, Japan.

Abstract

Background: The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC).

Methods: Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy.

Results: Heterogeneous enhancement patterns (Type-3 and -4), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern (Type-2) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS (p = 0.313). Because of significantly worse PPS, overall survival of Type-4 tumor was poor compared to Type-2 or -3 tumors (p = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01-0.71; p = 0.023), while Type-4 enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06-8.05; p = 0.039).

Conclusion: Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.

Keywords: Hepatocellular carcinoma; Lenvatinib; Lenvatinib-transarterial chemoembolization sequential therapy; Oncological aggressiveness; Subsequent treatment.