What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?
Authors: Atsushi Hiraoka, Takashi Kumada, Toshifumi Tada, Kazuya Kariyama, Joji Tani, Shinya Fukunishi, Masanori Atsukawa, Masashi Hirooka, Kunihiko Tsuji, Toru Ishikawa, Koichi Takaguchi, Ei Itobayashi, Kazuto Tajiri, Noritomo Shimada, Hiroshi Shibata, Hironori Ochi, Kazuhito Kawata, Satoshi Yasuda, Hidenori Toyoda, Hideko Ohama, Kazuhiro Nouso, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Korenobu Hayama, Taeang Arai, Michitaka Imai, Yohei Koizumi, Shinichiro Nakamura, Kouji Joko, Kojiro Michitaka, Yoichi Hiasa, Masatoshi Kudo
Journal: Liver Cancer (2021)

&lt;b&gt;&lt;i&gt;Background/Aim:&lt;/i&gt;&lt;/b&gt; An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], &lt;i&gt;n&lt;/i&gt; = 26; continued LEN beyond PD [B group], &lt;i&gt;n&lt;/i&gt; = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, &lt;i&gt;p&lt;/i&gt; = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, &lt;i&gt;p&lt;/i&gt; = 0.004), appearance of new extrahepatic metastasis (HR 2.396, &lt;i&gt;p&lt;/i&gt; = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001), and continuing LEN beyond PD (HR 0.297, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.