Lenvatinib (Lenvima,樂衛瑪)

HWT@ 2021/3/11

#作者建議

劑量需視情形調整(4-20 mg 每天) 。

目前臨床試驗進行中，有加上免疫治療藥物。

# 主要公布臨床試驗 

樂衛瑪(lenvatinib)用於標準化療難以治療的轉移性結直腸癌的II期研究：LEMON研究（NCCH1503）

#背景：

樂衛瑪，會抑制酪氨酸激酶( tyrosine kinases)，其包括

血管內皮生長因子（VEGF）受體(VEGFR)，成纖維細胞生長因子受體(FGFR)，血小板源性生長因子受體α，RET原癌基因和KIT原癌基因，受體酪氨酸激酶。

#評估標準化療失敗後 樂衛瑪在轉移性結直腸癌患者中的療效和安全性。

#患者：

單組的臨床2期研究。

符合條件的患者 

患有不可切除的轉移性結直腸腺癌，

對下列藥物有抗藥性:

5-FU，irinotecan(伊立替康)，oxaliplatin (奧沙利鉑)，Lonsurf (三氟吡啶/替吡西酯)，anti-VEGF (抗VEGF治療) 和 anit-EGFR (抗表皮生長因子受體治療)（用於野生型RAS腫瘤）。

#方法

在28天的周期中，每天一次以24 mg口服樂衛瑪治療患者，直至疾病進展或出現不可接受的毒性。

主要終點是集中評估疾病控制率。

次要終點包括安全性，緩解率，無進展生存期和總體生存期。

計劃的樣本量為30位患者，預期疾病控制率為60％，閾值疾病控制率為35％，單側alpha為5％，功效為80％

#結果：

2016年10月24日至2018年1月23日，30患者入組；

11例（37％）和19例（63％）分別接受過3或≥4例行轉移性化療的化療。

樂衛瑪週期的中位數為4（範圍1-13）。

疾病控制率為70.0％（21/30，90％CI 53.5％至83.4％，一側p = 0.0001）;

 2例患者有部分緩解，19例疾病穩定。

中位無進展生存期為3.6個月（95％CI為2.6至3.7）。中位總生存期為7.4個月（95％CI為6.4至10.8）。

最常見的≥3級不良事件為高血壓（53％），血小板減少症（10％），丙氨酸轉氨酶升高和厭食症（每種為7％）。

結論：標準化療失敗後，樂衛瑪表現出令人鼓舞的臨床活性，並被轉移性結直腸癌患者所耐受。

Phase II study of lenvatinib for metastatic colorectal cancer refractory to standard chemotherapy: the LEMON study (NCCH1503)

Satoru Iwasa # 1, Natsuko Okita # 1, Aya Kuchiba 2, Gakuto Ogawa 2, Mamiko Kawasaki 3, Kenichi Nakamura 3, Hirokazu Shoji 1, Yoshitaka Honma 1, Atsuo Takashima 1, Ken Kato 1, Tetsuya Hamaguchi 1, Narikazu Boku 1, Yasuhide Yamada 4 5

Affiliations expand

PMID: 32817132 PMCID: PMC7440718 DOI: 10.1136/esmoopen-2020-000776

Free PMC article

Abstract

Background: Lenvatinib inhibits tyrosine kinases, including vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor alpha, RET proto-oncogene and KIT proto-oncogene, receptor tyrosine kinase. We assessed the efficacy and safety of lenvatinib in patients with metastatic colorectal cancer after failure of standard chemotherapies.

Patients and methods: This was an open-label, single centre, single-arm, phase 2 study. Eligible patients had unresectable metastatic colorectal adenocarcinoma, refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, trifluridine/tipiracil, anti-VEGF therapy and anti-epidermal growth factor receptor therapy (for tumours with wild-type RAS). Patients were treated with oral lenvatinib at 24 mg one time a day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally assessed disease control rate. Secondary endpoints included safety, response rate, progression-free survival and overall survival. The planned sample size was 30 patients to expect a disease control rate of 60% with a threshold disease control rate of 35%, one-sided alpha of 5% and power of 80% RESULTS: Between 24 October 2016 and 23 January 2018, 30 patients were enrolled; 11 (37%) and 19 (63%) had received 3 or ≥4 lines of prior chemotherapy for metastatic disease, respectively. The median number of lenvatinib cycles was 4 (range 1-13). The centrally assessed disease control rate was 70.0% (21/30, 90% CI 53.5% to 83.4%, one-sided p=0.0001); 2 patients had a partial response and 19 had a stable disease. Median progression-free survival was 3.6 months (95% CI 2.6 to 3.7). Median overall survival was 7.4 months (95% CI 6.4 to 10.8). The most common grade ≥3 adverse events were hypertension (53%), thrombocytopenia (10%), increased alanine aminotransferase and anorexia (7% each).

Conclusions: Lenvatinib showed promising clinical activity and was tolerated in patients with metastatic colorectal cancer after failure of standard chemotherapies.