Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China

Abstract Background BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%–15% of acral or mucosal subtypes. Currently, immunotherapy with anti‐PD‐1 blockade and dual‐targeted therapy with Dabrafenib plus trametinib (D + T) target th...

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Main Authors: Jingqin Zhong, Wei Sun, Tu Hu, Chunmeng Wang, Wangjun Yan, Zhiguo Luo, Xin Liu, Yu Xu, Yong Chen
Format: Article
Language:English
Published: Wiley 2023-05-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.5866
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author Jingqin Zhong
Wei Sun
Tu Hu
Chunmeng Wang
Wangjun Yan
Zhiguo Luo
Xin Liu
Yu Xu
Yong Chen
author_facet Jingqin Zhong
Wei Sun
Tu Hu
Chunmeng Wang
Wangjun Yan
Zhiguo Luo
Xin Liu
Yu Xu
Yong Chen
author_sort Jingqin Zhong
collection DOAJ
description Abstract Background BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%–15% of acral or mucosal subtypes. Currently, immunotherapy with anti‐PD‐1 blockade and dual‐targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3‐year recurrence‐free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti‐PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF‐mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Methods Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow‐up of <6 months, or receiving other adjuvant treatment were excluded. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different adjuvant groups. Log‐rank analysis was used to identify prognostic factors for relapse‐free survival (RFS). Results Ninety‐three patients with resected stage III melanoma with BRAF V600E mutation were identified in our study, including 25 patients receiving adjuvant anti‐PD‐1 immunotherapy (PD‐1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation‐only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse‐free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD‐1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti‐PD‐1 monotherapy also showed significantly worse relapse control (p = 0.032). Conclusions For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse‐free survival compared to observation only. Dual‐targeted D + T therapy may still be the best choice for adjuvant therapy because anti‐PD‐1 monotherapy has failed to report equivalent efficacy in real‐world practice.
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spelling doaj.art-b3199656f93a4f40a0ba6b50873bce702023-06-06T07:30:47ZengWileyCancer Medicine2045-76342023-05-011210114751148210.1002/cam4.5866Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in ChinaJingqin Zhong0Wei Sun1Tu Hu2Chunmeng Wang3Wangjun Yan4Zhiguo Luo5Xin Liu6Yu Xu7Yong Chen8Department of Musculoskeletal Surgery Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Musculoskeletal Surgery Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Musculoskeletal Surgery Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Musculoskeletal Surgery Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Musculoskeletal Surgery Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Medical Oncology Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Medical Oncology Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Musculoskeletal Surgery Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Musculoskeletal Surgery Fudan University Shanghai Cancer Center Shanghai ChinaAbstract Background BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%–15% of acral or mucosal subtypes. Currently, immunotherapy with anti‐PD‐1 blockade and dual‐targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3‐year recurrence‐free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti‐PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF‐mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Methods Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow‐up of <6 months, or receiving other adjuvant treatment were excluded. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different adjuvant groups. Log‐rank analysis was used to identify prognostic factors for relapse‐free survival (RFS). Results Ninety‐three patients with resected stage III melanoma with BRAF V600E mutation were identified in our study, including 25 patients receiving adjuvant anti‐PD‐1 immunotherapy (PD‐1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation‐only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse‐free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD‐1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti‐PD‐1 monotherapy also showed significantly worse relapse control (p = 0.032). Conclusions For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse‐free survival compared to observation only. Dual‐targeted D + T therapy may still be the best choice for adjuvant therapy because anti‐PD‐1 monotherapy has failed to report equivalent efficacy in real‐world practice.https://doi.org/10.1002/cam4.5866adjuvant therapyBRAF mutationDabrafenibmelanomaPD‐1 inhibitorTrametinib
spellingShingle Jingqin Zhong
Wei Sun
Tu Hu
Chunmeng Wang
Wangjun Yan
Zhiguo Luo
Xin Liu
Yu Xu
Yong Chen
Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China
Cancer Medicine
adjuvant therapy
BRAF mutation
Dabrafenib
melanoma
PD‐1 inhibitor
Trametinib
title Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China
title_full Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China
title_fullStr Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China
title_full_unstemmed Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China
title_short Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China
title_sort comparative analysis of adjuvant therapy for stage iii braf mut melanoma a real world retrospective study from single center in china
topic adjuvant therapy
BRAF mutation
Dabrafenib
melanoma
PD‐1 inhibitor
Trametinib
url https://doi.org/10.1002/cam4.5866
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