Adjuvant therapy with anti-PD-1 antibody <italic style="font-style: italic">vs</italic> targeted therapy for patients with resected stage Ⅲ malignant melanoma: a real-world data analysis from China centers

Ting LI; Yu XU; Dongdong JIA; Zhichao LIAO; Wei SUN; Haixiao WU; Zhiwu REN; Jun ZHAO; Ruwei XING; Sheng TENG; Yun YANG; Yong CHEN; Tao LI; Jilong YANG

doi:10.19401/j.cnki.1007-3639.2022.12.002

您当前的位置：

首页 >

文章列表页 >

Adjuvant therapy with anti-PD-1 antibody vs targeted therapy for patients with resected stage Ⅲ malignant melanoma: a real-world data analysis from China centers

Specialists' Article | 更新时间：2025-12-31

- Adjuvant therapy with anti-PD-1 antibody vs targeted therapy for patients with resected stage Ⅲ malignant melanoma: a real-world data analysis from China centers
- China Oncology Vol. 32, Issue 12, Pages: 1147-1157(2022)
- 作者机构：
  
  1. 天津医科大学肿瘤医院骨与软组织肿瘤科，国家恶性肿瘤临床医学研究中心，天津 300060
  2. 天津市恶性肿瘤临床医学研究中心，天津市肿瘤防治重点实验室，天津市肿瘤分子流行病重点实验室，天津 300060
  3. 复旦大学附属肿瘤医院骨与软组织外科，复旦大学上海医学院肿瘤学系，上海 200032
  4. 中国科学院大学附属肿瘤医院（浙江省肿瘤医院）骨与软组织肿瘤科，浙江杭州 310022
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.12.002
  CLC： R739.5
- Received：26 September 2022，
  
  Revised：2022-11-29，
  
  Published：30 December 2022
- 稿件说明：
移动端阅览
Ting LI, Yu XU, Dongdong JIA, et al. Adjuvant therapy with anti-PD-1 antibody vs targeted therapy for patients with resected stage Ⅲ malignant melanoma: a real-world data analysis from China centers[J]. China Oncology, 2022, 32(12): 1147-1157.
DOI：

Ting LI, Yu XU, Dongdong JIA, et al. Adjuvant therapy with anti-PD-1 antibody vs targeted therapy for patients with resected stage Ⅲ malignant melanoma: a real-world data analysis from China centers[J]. China Oncology, 2022, 32(12): 1147-1157. DOI： 10.19401/j.cnki.1007-3639.2022.12.002.

摘要

背景与目的：

众多的临床试验结果表明，抗程序性死亡[蛋白

]

-1（programmed death-1，PD-1）治疗及靶向治疗均可显著延长Ⅲ期恶性黑色素瘤患者术后的无复发生存时间（recurrence-free survival，RFS）。然而，抗PD-1辅助治疗在中国真实世界中的治疗效果尚未见文献报道。本研究旨在总结分析中国Ⅲ期恶性黑色素瘤患者术后接受抗PD-1辅助治疗的RFS，并与

BRAF

V600

抑制剂vemurafenib进行初步对比分析。

方法：

回顾性分析2018年8月30日—2020年8月30日来自中国3所癌症中心的120例已经切除的Ⅲ期恶性黑色素瘤患者的临床信息。这些患者都接受了术后辅助性的pembrolizumab/toripalimab或vemurafenib治疗。采用Kaplan-Meier曲线评估RFS，采用log-r

ank检验来判断差异是否有统计学意义。

结果：

在接受辅助性抗PD-1治疗的90例Ⅲ期恶性黑色素瘤患者中，中位RFS（median-RFS，mRFS）为16个月（95% CI：14~18个月）；12个月RFS率为69.5%（95% CI：64.6%~74.4%），24个月RFS率为45.8%（95% CI：40.5%~51.1%）。30例接受vemurafenib治疗的Ⅲ期恶性黑色素瘤患者中，mRFS为18个月（95% CI：10~21个月），12个月RFS率为62.8%（95% CI：54.0%~71.6%），24个月RFS率为35.9%（95% CI：27.1%~44.7%）。分层分析初步结果显示，抗PD-1治疗组和vemurafenib组的RFS没有明显差异。其次，

BRAF

V600E

是否突变可能不影响抗PD-1治疗的RFS。另外，在本研究中，对于

BRAF

V600E

突变的患者，术后接受抗PD-1治疗或vemurafenib，其RFS差异无统计学意义。最后，虽然皮肤型恶性黑色素瘤患者的RFS优于肢端型患者，来源不明患者的RFS最差，但在中国真实世界中，抗PD-1辅助治疗的治疗效果仍较差。

结论：

作为中国Ⅲ期恶性黑色素瘤患者辅助抗PD-1治疗的真实世界数据，在本研究中，辅助性抗PD-1治疗与辅助vemurafenib治疗效果的差异并无统计学意义，提示对于中国Ⅲ期恶性黑色素瘤患者，我们可能仍然需要探索更多的联合治疗来改善其辅助治疗的效果。

Abstract

Background and purpose:

Anti-programmed death-1 (anti-PD-1) adjuvant therapy and targeted therapy have resulted in longer recurrence-free survival (RFS) for malignant melanoma patients in clinical trials. However

the efficacy of adjuvant anti-PD-1 therapy in Chinese melanoma patients has not been previously reported. The purpose of this study was to retrospectively analyze the RFS in Chinese resected stage Ⅲ malignant melanoma patients treated with adjuvant anti-PD-1 therapy and to preliminarily compare it with

BRAF

V600

inhibitor vemurafenib.

Methods:

This study retrospectively collected the information of 120 patients with resected stage Ⅲ malignant melanoma from three major cancer centers in China from August 30

2018 to August 30

2020. These patients received adjuvant pembrolizumab/toripalimab or vemurafenib. RFS rates were assessed by Kaplan-Meier curves and log-rank tests were used to examined differences.

Results:

Among the 90 patients with stage Ⅲ malignant melanoma receiving adjuvant anti-PD-1 therapy

the median-RFS (mRFS) was 16 months (95% CI: 14-18 months); the 12-month RFS rate was 69.5% (95% CI: 64.6%-74.4%) and the 24-month RFS rate was 45.8% (95% CI

: 40.5%-51.1%). The mRFS for 30 patients who received vemurafenib was 18 months (95% CI: 10-21 months)

the 12-month RFS rate was 62.8% (95% CI: 54.0%-71.6%)

and the 24-month RFS rate was 32.9% (95% CI: 27.1%-44.7%). In the stratified analysis

firstly

there was no difference in RFS between anti-PD-1 therapy group and vemurafenib group. Secondly

the

BRAF

V600E

mutation status may did not affect the RFS of anti-PD-1 therapy. In addition

in this study

for the patients with

BRAF

V600E

mutation

the RFS showed no difference between these patients received anti-PD-1 therapy or vemurafenib. Finally

although the RFS was better in patients with cutaneous melanoma than in patients with acral and worst in patients of unknown origin

the data for adjuvant therapy in China were still poor.

Conclusion:

These are the real-world data from adjuvant anti-PD-1 therapy in patients with resected stage Ⅲ cutaneous and acral melanoma patients in China. In our study

adjuvant anti-PD-1 therapy is indistinguishable from vemurafenib indicates more combination therapies are needed to improve outcome in China.

关键词

Keywords

references

SIEGEL R L , MILLER K D , FUCHS H E , et al . Cancer statistics, 2021 [J ] . CA A Cancer J Clin , 2021 , 71 ( 1 ): 7 - 33 . DOI: 10.3322/caac.21654 http://doi.org/10.3322/caac.21654 https://onlinelibrary.wiley.com/doi/10.3322/caac.21654 https://onlinelibrary.wiley.com/doi/10.3322/caac.21654

HAO M Z , ZHAO G , DU X L , et al . Clinical characteristics and prognostic indicators for metastatic melanoma: data from 446 patients in North China [J ] . Tumour Biol , 2016 , 37 ( 8 ): 10339 - 10348 . DOI: 10.1007/s13277-016-4914-4 http://doi.org/10.1007/s13277-016-4914-4 http://link.springer.com/10.1007/s13277-016-4914-4 http://link.springer.com/10.1007/s13277-016-4914-4

CHEN W Q , ZHENG R S , BAADE P D , et al . Cancer statistics in China, 2015 [J ] . CA A Cancer J Clin , 2016 , 66 ( 2 ): 115 - 132 . DOI: 10.3322/caac.21338 http://doi.org/10.3322/caac.21338 http://doi.wiley.com/10.3322/caac.21338 http://doi.wiley.com/10.3322/caac.21338

SVEDMAN F C , PILLAS D , TAYLOR A , et al . Stage-specific survival and recurrence in patients with cutaneous malignant melanoma in Europe - a systematic review of the literature [J ] . Clin Epidemiol , 2016 , 8 : 109 - 122 . DOI: 10.2147/CLEP.S99021 http://doi.org/10.2147/CLEP.S99021

KIRKWOOD J M , IBRAHIM J G , SONDAK V K , et al . High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190 [J ] . J Clin Oncol , 2000 , 18 ( 12 ): 2444 - 2458 . DOI: 10.1200/JCO.2000.18.12.2444 http://doi.org/10.1200/JCO.2000.18.12.2444

EGGERMONT A M , SUCIU S , MACKIE R , et al . Post-surgery adjuvant therapy with intermediate doses of interferon Alfa 2b versus observation in patients with stage Ⅱb/Ⅲ melanoma (EORTC 18952): randomised controlled trial [J ] . Lancet , 2005 , 366 ( 9492 ): 1189 - 1196 . DOI: 10.1016/S0140-6736(05)67482-X http://doi.org/10.1016/S0140-6736(05)67482-X https://linkinghub.elsevier.com/retrieve/pii/S014067360567482X https://linkinghub.elsevier.com/retrieve/pii/S014067360567482X

CHAPMAN P B , HAUSCHILD A , ROBERT C , et al . Improved survival with vemurafenib in melanoma with BRAF V600E mutation [J ] . N Engl J Med , 2011 , 364 ( 26 ): 2507 - 2516 . DOI: 10.1056/NEJMoa1103782 http://doi.org/10.1056/NEJMoa1103782 http://www.nejm.org/doi/abs/10.1056/NEJMoa1103782 http://www.nejm.org/doi/abs/10.1056/NEJMoa1103782

EGGERMONT A M M , BLANK C U , MANDALA M , et al . Longer follow-up confirms recurrence-free survival benefit of adjuvant pembrolizumab in high-risk stage Ⅲ melanoma: updated results from the EORTC 1325-MG/KEYNOTE-054 trial [J ] . J Clin Oncol , 2020 , 38 ( 33 ): 3925 - 3936 . DOI: 10.1200/JCO.20.02110 http://doi.org/10.1200/JCO.20.02110 https://ascopubs.org/doi/10.1200/JCO.20.02110 https://ascopubs.org/doi/10.1200/JCO.20.02110

DUMMER R , HAUSCHILD A , SANTINAMI M , et al . Five-year analysis of adjuvant dabrafenib plus trametinib in stage Ⅲ melanoma [J ] . N Engl J Med , 2020 , 383 ( 12 ): 1139 - 1148 . DOI: 10.1056/NEJMoa2005493 http://doi.org/10.1056/NEJMoa2005493 http://www.nejm.org/doi/10.1056/NEJMoa2005493 http://www.nejm.org/doi/10.1056/NEJMoa2005493

DAVIES H , BIGNELL G R , COX C , et al . Mutations of the BRAF gene in human cancer [J ] . Nature , 2002 , 417 ( 6892 ): 949 - 954 . DOI: 10.1038/nature00766 http://doi.org/10.1038/nature00766 https://doi.org/10.1038/nature00766 https://doi.org/10.1038/nature00766

IKAWA S , FUKUI M , UEYAMA Y , et al . B-raf, a new member of the raf family, is activated by DNA rearrangement [J ] . Mol Cell Biol , 1988 , 8 ( 6 ): 2651 - 2654 . DOI: 10.1128/mcb.8.6.2651-2654.1988 http://doi.org/10.1128/mcb.8.6.2651-2654.1988

MAIO M , LEWIS K , DEMIDOV L , et al . Adjuvant vemurafenib in resected, BRAF V600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial [J ] . Lancet Oncol , 2018 , 19 ( 4 ): 510 - 520 . DOI: 10.1016/S1470-2045(18)30106-2 http://doi.org/10.1016/S1470-2045(18)30106-2 https://linkinghub.elsevier.com/retrieve/pii/S1470204518301062 https://linkinghub.elsevier.com/retrieve/pii/S1470204518301062

FLAHERTY K T , INFANTE J R , DAUD A , et al . Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations [J ] . N Engl J Med , 2012 , 367 ( 18 ): 1694 - 1703 . DOI: 10.1056/NEJMoa1210093 http://doi.org/10.1056/NEJMoa1210093 http://www.nejm.org/doi/abs/10.1056/NEJMoa1210093 http://www.nejm.org/doi/abs/10.1056/NEJMoa1210093

BAI X , SHOUSHTARI A N , BETOF WARNER A , et al . Discrepancies in response and immune-related adverse events (IrAE) of anti-PD-1 monotherapy between races and primary sites in patients (pts) with advanced nonacral cutaneous melanoma (NACM) [J ] . J Clin Oncol , 2021 , 39 ( 15_suppl ): 9530 . DOI: 10.1200/JCO.2021.39.15_suppl.9530 http://doi.org/10.1200/JCO.2021.39.15_suppl.9530 https://ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.9530 https://ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.9530

LI T , JIA D D , TENG L S . Adjuvant pembrolizumab versus high-dose interferon α-2b for Chinese patients with resected stage Ⅲ melanoma: a retrospective cohort study [J ] . Invest New Drugs , 2020 , 38 ( 5 ): 1334 - 1341 . DOI: 10.1007/s10637-020-00913-6 http://doi.org/10.1007/s10637-020-00913-6 https://doi.org/10.1007/s10637-020-00913-6 https://doi.org/10.1007/s10637-020-00913-6

JIA D D , NIU Y L , ZHU H L , et al . Prior therapy with pegylated-interferon alfa-2b improves the efficacy of adjuvant pembrolizumab in resectable advanced melanoma [J ] . Front Oncol , 2021 , 11 : 675873.

GAO T F , LIU J , WU J . Cost-effectiveness analysis of dabrafenib plus trametinib and vemurafenib as first-line treatment in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma in China [J ] . Int J Environ Res Public Health , 2021 , 18 ( 12 ): 6194 . DOI: 10.3390/ijerph18126194 http://doi.org/10.3390/ijerph18126194 https://www.mdpi.com/1660-4601/18/12/6194 https://www.mdpi.com/1660-4601/18/12/6194

NAMIKAWA K , YAMAZAKI N . Targeted therapy and immunotherapy for melanoma in Japan [J ] . Curr Treat Options Oncol , 2019 , 20 ( 1 ): 7 . DOI: 10.1007/s11864-019-0607-8 http://doi.org/10.1007/s11864-019-0607-8 https://doi.org/10.1007/s11864-019-0607-8 https://doi.org/10.1007/s11864-019-0607-8

SI L , KONG Y , XU X W , et al . Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort [J ] . Eur J Cancer , 2012 , 48 ( 1 ): 94 - 100 .

HAMID O , ROBERT C , DAUD A , et al . Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001 [J ] . Ann Oncol , 2019 , 30 ( 4 ): 582 - 588 . DOI: S0923-7534(19)31110-X http://doi.org/S0923-7534(19)31110-X

TOPALIAN S L , SZNOL M , MCDERMOTT D F , et al . Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab [J ] . J Clin Oncol , 2014 , 32 ( 10 ): 1020 - 1030 . DOI: 10.1200/JCO.2013.53.0105 http://doi.org/10.1200/JCO.2013.53.0105

SI L , ZHANG X S , SHU Y Q , et al . A phase ib study of pembrolizumab as second-line therapy for Chinese patients with advanced or metastatic melanoma (KEYNOTE-151) [J ] . Transl Oncol , 2019 , 12 ( 6 ): 828 - 835 . DOI: S1936-5233(18)30591-6 http://doi.org/S1936-5233(18)30591-6

Views

2602

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Progress and future prospects in local and systemic treatment of early breast cancer

Expert consensus on perioperative comprehensive treatment for high risk prostate cancer (2023 edition)

Current status and prospect of perioperative treatment of stage Ⅲ melanoma

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

Expert consensus on metformin adjuvant therapy in malignant tumor patients with diabetes mellitus type 2 (2022 edition)

Related Author

Junjie LI

of Male Reproductive System Oncology Society

Anti-Cancer Association China

Yu XU

Yong CHEN

Jilong YANG

Guannan ZHU

Dongdong JIA

Related Institution

Department of Breast Surgery, Fudan University Shanghai Cancer Center/Fudan University Breast Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University

Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University

Department of Dermatology, Xijing Hospital, Air Force Military Medical University (Fourth Military Medical University)

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

Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

AI问答

⁰

Adjuvant therapy with anti-PD-1 antibody vs targeted therapy for patients with resected stage Ⅲ malignant melanoma: a real-world data analysis from China centers

DOI：10.19401/j.cnki.1007-3639.2022.12.002

摘要

Abstract

关键词

Keywords

references