达拉非尼联合曲美替尼用于24例恶性黑色素瘤辅助治疗的回顾性分析

doi:10.19401/j.cnki.1007-3639.2022.12.005

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (12): 1178-1183.doi: 10.19401/j.cnki.1007-3639.2022.12.005

达拉非尼联合曲美替尼用于24例恶性黑色素瘤辅助治疗的回顾性分析

贾东东(), 李涛()

中国科学院大学附属肿瘤医院（浙江省肿瘤医院）骨与软组织肿瘤外科，中国科学院基础医学与肿瘤研究所，浙江杭州 310005

收稿日期:2022-11-09 修回日期:2022-12-01 出版日期:2022-12-30 发布日期:2023-02-02
通信作者: 李涛（ORCID：0000-0002-5924-0522）。
作者简介:贾东东（ORCID：0000-0002-6804-4988）。
李涛，医学博士，主任医师，教授。现任中国科学院大学附属肿瘤医院（浙江省肿瘤医院）骨与软组织肿瘤外科主任，浙江省癌症中心恶性黑色素瘤诊治中心主任。担任中国抗癌协会肉瘤专业委员会常委、软组织肿瘤学组副组长，中国抗癌协会皮肤肿瘤专业委员会常委，浙江省抗癌协会皮肤肿瘤专业委员会主任委员，浙江省抗癌协会骨与软组织肿瘤专业委员会副主任委员，中国继续医学教育协会骨与软组织肿瘤专业委员会常委等。荣获浙江省高层次创新人才称号。此外担任《皮肤及肢端恶性黑色素瘤外科诊治中国专家共识》主编，《中国软组织肿瘤专家共识》《中国临床肿瘤学会CSCO常见恶性肿瘤诊疗指南》编委。擅长各种骨与软组织良恶性肿瘤的治疗，包括骨恶性肿瘤的关节置换等保肢手术，软组织肉瘤的广泛切除及术后缺损的各种肌皮瓣转移修复重建，骨盆、骶骨肿瘤切除及功能重建，脊柱转移癌的手术及综合治疗等。

Retrospective analysis of adjuvant therapy with dabrafenib and trametinib for 24 patients with malignant melanoma

JIA Dongdong(), LI Tao()

Department of Bone and Soft-tissue Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310005, Zhejiang Province, China

Received:2022-11-09 Revised:2022-12-01 Published:2022-12-30 Online:2023-02-02
Contact: LI Tao

摘要/Abstract

摘要：

背景与目的：恶性黑色素瘤是最致命的皮肤恶性肿瘤。Ⅲ期黑色素瘤术后复发的风险相对较高，本文回顾性分析了达拉非尼联合曲美替尼作为辅助治疗对携带有BRAF突变的中国Ⅲ期恶性黑色素瘤患者的疗效及安全性。方法：回顾性分析2019年8月—2022年4月在浙江省肿瘤医院收治的24例接受曲美替尼联合达拉非尼辅助治疗的Ⅲ期皮肤及肢端恶性黑色素瘤的患者。结果：在24例患者中，7例为黑色素瘤ⅢB期，11例为ⅢC期，3例为ⅢD期，3例为Ⅲ期（具体分期不明）。截至2022年10月1日，有12例（50.0%）患者完成了1年的辅助治疗。全部24例患者中有5例（20.8%）报告肿瘤复发。1年无复发生存（relapse-free survival，RFS）率为76.2%（95% CI：65.2% ~ 87.2%）。在皮肤黑色素瘤亚组中，1年RFS率为81.6%（95% CI：71.6% ~ 91.6%）。2例在辅助治疗期间复发，3例患者在完成治疗方案后复发。20例患者（83.3%）报告了至少一次不良事件，其中7例患者（29.2%）发生了3级或4级的严重不良反应。最常见的不良反应是发热、疲劳和恶心。有4例患者发生了脂膜炎，主要累及大腿及上肢。1例患者（4.2%）因不良事件导致永久停药，2例患者（8.3%）因不良事件导致剂量调整，7例患者（29.2%）因不良事件导致用药中断。结论：本研究结果显示，达拉非尼联合曲美替尼辅助治疗可使BRAF ^V600突变的Ⅲ期黑色素瘤患者短期获益，耐受性良好。

关键词: 恶性黑色素瘤, 辅助治疗, 靶向治疗, 有效性, 安全性

Abstract:

Background and purpose: Melanoma is the most lethal cutaneous malignant tumor. Patients with resected stage Ⅲ melanomas have a high risk of recurrence after surgery. This study retrospectively analyzed the efficacy and safety of dabrafenib combined with trametinib in the adjuvant setting for stage Ⅲ melanoma patients with BRAF mutation in China. Methods: A retrospective analysis was performed on 24 patients with stage Ⅲ cutaneous and acral malignant melanoma who received adjuvant treatment with trametinib and dabrafenib in Zhejiang Cancer Hospital from August 2019 to April 2022. Results: Of the 24 patients, 7 were stage Ⅲ B, 11 were stage Ⅲ C, 3 were stage Ⅲ D, and 3 were stage Ⅲ (the specific stage was unknown). As of October 1, 2022, 12 patients (50.0%) had completed the protocol for one year. Of the 24 patients, 5 (20.8%) patients relapsed. The The 1-year recurrence-free survival (RFS) rate was 76.2% (95% CI: 65.2%-87.2%). In the cutaneous melanoma subgroup, the 1-year RFS rate was 81.6% (95% CI: 71.6%-91.6%). Two patients relapsed during adjuvant therapy, and three patients relapsed after completing the protocol. Twenty patients (83.3%) reported at least one adverse event, of which 7 patients (29.2%) had grade 3 or grade 4 serious adverse reactions. The most common adverse reactions were fever, fatigue and nausea. Panniculitis occurred in 4 patients, mainly involving thighs and upper limbs. One patient (4.2%) permanently stopped taking the drug due to adverse events, the dose was adjusted in 2 patients (8.3%) due to adverse events, and drug treatment was interrupted in 7 patients (29.2%) due to adverse events. Conclusion: This study confirmed the short-term benefit and good tolerance of the adjuvant therapy with dabrafenib combined with trametinib in Chinese patients with stage Ⅲ melanoma with BRAF^V600 mutation.

Key words: Malignant melanoma, Adjuvant therapy, Targeted therapy, Effectiveness, Safety

中图分类号:

R739.5

贾东东, 李涛. 达拉非尼联合曲美替尼用于24例恶性黑色素瘤辅助治疗的回顾性分析[J]. 中国癌症杂志, 2022, 32(12): 1178-1183.

JIA Dongdong, LI Tao. Retrospective analysis of adjuvant therapy with dabrafenib and trametinib for 24 patients with malignant melanoma[J]. China Oncology, 2022, 32(12): 1178-1183.

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参考文献 21

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Variable	Number and proportion n (%)
Gender
Male	7 (29.2)
Female	17 (70.8)
Histology
Cutaneous	20 (83.3)
Acral	3 (12.5)
Unknown	1 (4.2)
Stage
ⅢB	7 (29.2)
ⅢC	11 (45.8)
ⅢD	3 (12.5)
Ⅲ unspecified	3 (12.5)
Primary tumor ulceration
Yes	10 (41.7)
No	12 (50)
Unknown	2 (8.3)
BRAF status
V600E	22 (91.7)
V600K	2 (8.2)

Adverse event	Any grade	Grade 3 or 4
Any adverse event	20 (83.3)	7 (29.2)
Pyrexia	18 (75.0)	6 (25.0)
Fatigue	8 (33.3)	1 (4.2)
Nausea	7 (29.2)	1 (4.2)
Headache	7 (29.2)	1 (4.2)
Chills	6 (25.0)	0 (0.0)
Diarrhea	6 (25.0)	0 (0.0)
Rash	5 (20.8)	0 (0.0)
Vomiting	4 (16.7)	1 (4.2)
Arthralgia	4 (16.7)	0 (0.0)
Panniculitis	4 (16.7)	0 (0.0)
Cough	4 (16.7)	0 (0.0)
Elevated alanine aminotransferase	3 (12.5)	0 (0.0)
Elevated aspartate aminotransferase	3 (12.5)	0 (0.0)
Peripheral edema	2 (8.3)	0 (0.0)
Constipation	2 (8.3)	0 (0.0)
Hypertension	1 (4.2)	0 (0.0)
Decreased appetite	1 (4.2)	0 (0.0)
Erythema	1 (4.2)	0 (0.0)

达拉非尼联合曲美替尼用于24例恶性黑色素瘤辅助治疗的回顾性分析

Retrospective analysis of adjuvant therapy with dabrafenib and trametinib for 24 patients with malignant melanoma

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