Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib

被引：18

作者：

Rapposelli, Ilario Giovanni ^{[1
]}

Tada, Toshifumi ^{[2
]}

Shimose, Shigeo ^{[3
]}

Burgio, Valentina ^{[4
]}

Kumada, Takashi ^{[5
]}

Iwamoto, Hideki ^{[3
]}

Hiraoka, Atsushi ^{[6
]}

Niizeki, Takashi ^{[3
]}

Atsukawa, Masanori ^{[7
]}

Koga, Hironori ^{[3
]}

Hirooka, Masashi ^{[8
]}

Torimura, Takuji ^{[3
]}

Iavarone, Massimo ^{[9
]}

Tortora, Raffaella ^{[10
]}

Campani, Claudia ^{[11
]}

Lonardi, Sara ^{[12
,13
]}

Tamburini, Emiliano ^{[14
]}

Piscaglia, Fabio ^{[15
]}

Masi, Gianluca ^{[16
]}

Cabibbo, Giuseppe ^{[17
]}

Giuseppe Foschi, Francesco ^{[18
]}

Silletta, Marianna ^{[19
]}

Tsuji, Kunihiko ^{[20
]}

Ishikawa, Toru ^{[21
]}

Takaguchi, Koichi ^{[22
]}

Kariyama, Kazuya ^{[23
]}

Itobayashi, Ei ^{[24
]}

Tajiri, Kazuto ^{[25
]}

Shimada, Noritomo ^{[26
]}

Shibata, Hiroshi ^{[27
]}

Ochi, Hironori ^{[28
]}

Yasuda, Satoshi ^{[29
]}

Toyoda, Hidenori ^{[29
]}

Fukunishi, Shinya ^{[30
]}

Ohama, Hideko ^{[30
]}

Kawata, Kazuhito ^{[31
]}

Tani, Joji ^{[32
]}

Nakamura, Shinichiro ^{[2
]}

Nouso, Kazuhiro ^{[23
]}

Tsutsui, Akemi ^{[22
]}

Nagano, Takuya ^{[22
]}

Tanaka, Takaaki ^{[6
]}

Itokawa, Norio ^{[7
]}

Okubo, Tomomi ^{[7
]}

Arai, Taeang ^{[7
]}

Imai, Michitaka ^{[21
]}

Joko, Kouji ^{[28
]}

Koizumi, Yohei ^{[8
]}

Hiasa, Yoichi ^{[8
]}

Rimini, Margherita ^{[33
]}

机构：

[1] IRCCS Ist Romagnolo Studio Tumori Dino Amadori IR, Dept Med Oncol, Meldola, Italy

[2] Japanese Red Cross Himeji Hosp, Dept Internal Med, Himeji, Hyogo, Japan

[3] Kurume Univ, Div Gastroenterol, Dept Med, Sch Med, Kurume, Fukuoka, Japan

[4] San Raffaele Sci Inst IRCCS, Dept Med Oncol, Milan, Italy

[5] Gifu Kyoritsu Univ, Fac Nursing, Ogaki, Japan

[6] Ehime Prefectural Cent Hosp, Gastroenterol Ctr, Matsuyama, Ehime, Japan

[7] Nippon Med Sch, Div Gastroenterol & Hepatol, Dept Internal Med, Tokyo, Japan

[8] Ehime Univ, Dept Gastroenterol & Metabol, Grad Sch Med, Matsuyama, Ehime, Japan

[9] Fdn IRCCS Ca Granda Osped Maggiore Policlin Milan, Div Gastroenterol & Hepatol, Milan, Italy

[10] Cardarelli Hosp, Liver Unit, Naples, Italy

[11] Univ Florence, Dept Expt & Clin Biomed Sci Mario Serio, Florence, Italy

[12] Veneto Inst Oncol IOV IRCCS, Dept Oncol, Early Phase Clin Trial Unit, Padua, Italy

[13] Veneto Inst Oncol IOV IRCCS, Dept Oncol, Med Oncol Unit 1, Padua, Italy

[14] Card G Panico Hosp Tricase, Dept Med Oncol, Tricase, Italy

[15] Azienda Osped Univ Bologna, Div Internal Med Hepatobiliary & Immunoallerg Dis, Bologna, Italy

[16] Azienda Osped Univ Pisana, Pisa, Italy

[17] Univ Palermo, Gastroenterol & Hepatol Unit, Dept Hlth Promot Mother & Child Care, Internal Med & Med Specialties,PROMISE, Palermo, Italy

[18] Faenza Hosp, Dept Internal Med, AUSL Romagna, Faenza, Italy

[19] Univ Campus Bio Medico, Med Oncol Unit, Rome, Italy

[20] Teine Keijinkai Hosp, Ctr Gastroenterol, Sapporo, Hokkaido, Japan

[21] Saiseikai Niigata Hosp, Dept Gastroenterol, Niigata, Japan

[22] Kagawa Prefectural Cent Hosp, Dept Hepatol, Takamatsu, Kagawa, Japan

[23] Okayama City Hosp, Dept Gastroenterol, Okayama, Japan

[24] Asahi Gen Hosp, Dept Gastroenterol, Asahi, Japan

[25] Toyama Univ Hosp, Dept Gastroenterol, Toyama, Japan

[26] Otakanomori Hosp, Div Gastroenterol & Hepatol, Kashiwa, Chiba, Japan

[27] Tokushima Prefectural Cent Hosp, Dept Gastroenterol, Tokushima, Japan

[28] Matsuyama Red Cross Hosp, Hepatobiliary Ctr, Matsuyama, Ehime, Japan

[29] Ogaki Municipal Hosp, Dept Gastroenterol & Hepatol, Ogaki, Japan

[30] Osaka Med Coll, Dept Internal Med 2, Takatsuki, Osaka, Japan

[31] Hamamatsu Univ, Hepatol Div, Dept Internal Med, Sch Med, Hamamatsu, Shizuoka, Japan

[32] Kagawa Univ, Dept Gastroenterol & Neurol, Sch Med, Takamatsu, Kagawa, Japan

[33] Univ Hosp Modena, Dept Hematol & Oncol, Div Oncol, Modena, Italy

[34] IRCCS San Raffaele Sci Inst, Hepatobiliary Surg Div, Milan, Italy

[35] Univ Vita Salute San Raffaele, Milan, Italy

来源：

LIVER INTERNATIONAL | 2021年 / 41卷 / 12期

关键词：

adverse events; hepatocellular carcinoma; lenvatinib; predictive factors; SORAFENIB; HYPERTENSION; SURVIVAL; EFFICACY; OUTCOMES; REFLECT; SAFETY; IMPACT;

D O I：

10.1111/liv.15014

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background and Aim Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. Methods We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). Results The appearance of arterial hypertension G >= 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased appetite G >= 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), whereas decreased appetite G >= 2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, P = .0277). Conclusions Our main findings are that the occurrence of arterial hypertension G >= 2 is a predictor of longer survival, whereas decreased appetite G >= 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.

引用

页码：2997 / 3008

页数：12