Early Tumor Shrinkage as a Predictive Factor for Outcomes in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Analysis.

Aya Takahashi,Takeshi Okanoue,Hiroyuki Kimura,Hironori Mitsuyoshi,Yuya Seko,Kanji Yamaguchi,Yasuhide Mitsumoto,Akira Okajima,Akira Muramatsu,Taichiro Nishikawa,Atsushi Umemura,Masahiro Arai,Tasuku Hara,Michihisa Moriguchi,Atsuhiro Morita,Takaharu Yo,Hidetaka Takashima,Hiroki Ishikawa,Naomi Yoshinami,Masayasu Jo,Yoshito Itoh,Hideki Fujii,Yasuyuki Nagao,Hiroshi Ishiba,Tomoki Nakajima,Toshihide Shima

doi:10.3390/cancers12030754

Abstract

We investigated the association between early tumor shrinkage (ETS) and treatment outcome in patients with hepatocellular carcinoma treated with lenvatinib (LEN). A retrospective analysis was performed in 104 patients. ETS was defined as tumor shrinkage at the first evaluation in the sum of target lesions’ longest diameters from baseline according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 5.0 months. The receiver operating characteristic curve analysis in differentiating long-term responders (PFS ≥ 5.0 months) from short-term responders (PFS < 5.0 months) revealed an ETS cut-off value of 10%. ETS ≥ 10% was significantly correlated with better PFS and OS compared with ETS < 10%. Additionally, ETS ≥ 10% showed a better discrimination ability on prognosis compared with modified RECIST-based objective response at the first evaluation. Multivariate analysis confirmed ETS ≥ 10% as an independent predictor of better OS, as well as a Child–Pugh score of 5 and macrovascular invasion. In conclusion, ETS ≥ 10% was strongly associated with outcome in patients treated with LEN. This biomarker could allow earlier assessment of the treatment response and guide treatment decision-making for HCC.

Highlights

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the fourth leading cause of cancer-related death worldwide [1]
This study aimed to evaluate the prognostic role of early tumor shrinkage (ETS), as well as identify the optimal cut-off value of ETS in HCC patients treated with LEN
We considered that ETS ≥ 10% based on the Response Evaluation Criteria in Solid Tumors (RECIST) could be a more favorable predictive factor than the modified Response Evaluation Criteria in Solid Tumors (mRECIST)-based objective response at the first evaluation in terms of early indicator of survival outcome

Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the fourth leading cause of cancer-related death worldwide [1]. Because the symptoms of early HCC are often inconspicuous, most patients are diagnosed at an advanced stage, eliminating the option of local treatment, such as curative hepatic resection, tumor ablation, or transarterial therapy. Systemic treatment of advanced HCC is of great concern. A multikinase inhibitor, is the first targeted agent approved as first-line therapy for advanced HCC [2]. In the last two years, three successful novel drugs have emerged from clinical trials for clinical use, including lenvatinib (LEN) as a first-line treatment and regorafenib and ramucirumab as second-line treatments [3,4,5]. With the increasing number of therapeutic options, the need for effective early methods to evaluate treatment activity has become critical

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