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Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis

BACKGROUND: Mucosal melanoma is an aggressive melanoma subtype with poor response to antiprogrammed cell death-1 (PD-1) monotherapy. Axitinib in combination with toripalimab, a humanized IgG4 mAb against PD-1, showed a promising response rate in patients with metastatic mucosal melanoma (MM) in a ph...

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Autores principales: Li, Siming, Wu, Xiaowen, Yan, Xieqiao, Zhou, Li, Chi, Zhihong, Si, Lu, Cui, Chuanliang, Tang, Bixia, Mao, Lili, Lian, Bin, Wang, Xuan, Bai, Xue, Dai, Jie, Kong, Yan, Tang, Xiongwen, Feng, Hui, Yao, Sheng, Flaherty, Keith T, Guo, Jun, Sheng, Xinan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066368/
https://www.ncbi.nlm.nih.gov/pubmed/35193932
http://dx.doi.org/10.1136/jitc-2021-004036
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author Li, Siming
Wu, Xiaowen
Yan, Xieqiao
Zhou, Li
Chi, Zhihong
Si, Lu
Cui, Chuanliang
Tang, Bixia
Mao, Lili
Lian, Bin
Wang, Xuan
Bai, Xue
Dai, Jie
Kong, Yan
Tang, Xiongwen
Feng, Hui
Yao, Sheng
Flaherty, Keith T
Guo, Jun
Sheng, Xinan
author_facet Li, Siming
Wu, Xiaowen
Yan, Xieqiao
Zhou, Li
Chi, Zhihong
Si, Lu
Cui, Chuanliang
Tang, Bixia
Mao, Lili
Lian, Bin
Wang, Xuan
Bai, Xue
Dai, Jie
Kong, Yan
Tang, Xiongwen
Feng, Hui
Yao, Sheng
Flaherty, Keith T
Guo, Jun
Sheng, Xinan
author_sort Li, Siming
collection PubMed
description BACKGROUND: Mucosal melanoma is an aggressive melanoma subtype with poor response to antiprogrammed cell death-1 (PD-1) monotherapy. Axitinib in combination with toripalimab, a humanized IgG4 mAb against PD-1, showed a promising response rate in patients with metastatic mucosal melanoma (MM) in a phase Ib study. Here, we report the updated overall survival (OS), duration of response (DoR), and biomarker analysis results. METHODS: Patients with advanced MM received toripalimab 1 or 3 mg/kg intravenously every 2 weeks combined with axitinib 5 mg orally two times per day until disease progression or unacceptable toxicity. Tumor programmed cell death ligand-1 (PD-L1) expression, tumor mutational burden (TMB), and gene expression profile (GEP) by messenger RNA sequencing were evaluated for correlation with survival. RESULTS: As of April 2, 2021, the median follow-up was 42.5 months. Among 29 chemotherapy-naïve patients with metastatic MM, the median OS was 20.7 months (95% CI 9.7 to 32.7 months); the median progression-free survival (PFS) was 7.5 months (95% CI 3.8 to 14.8 months); and the median DoR was 13.4 months (95% CI 5.5 to 20.6 months). The OS rates of 1, 2, and 3 years were 62.1%, 44.8%, and 31.0%, respectively. Biomarker analysis found that PD-L1 expression and TMB level were not associated with survival benefits. In contrast, a 12-GEP signature correlated with improved PFS (17.7 vs 5.7 months, p=0.0083) and OS (35.6 vs 17.6 months, p=0.039). CONCLUSIONS: The 3-year survival update confirmed the antitumor activity and long-term survival benefit of the toripalimab plus axitinib combination in patients with advanced MM. The 12-gene GEP is of value in predicting the outcomes of vascular endothelial growth factor receptor-tyrosine kinase inhibitor and PD-1 blockade combination therapy, but requires further validation. TRIAL REGISTRATION NUMBERS: NCT03086174.
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spelling pubmed-90663682022-05-12 Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis Li, Siming Wu, Xiaowen Yan, Xieqiao Zhou, Li Chi, Zhihong Si, Lu Cui, Chuanliang Tang, Bixia Mao, Lili Lian, Bin Wang, Xuan Bai, Xue Dai, Jie Kong, Yan Tang, Xiongwen Feng, Hui Yao, Sheng Flaherty, Keith T Guo, Jun Sheng, Xinan J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: Mucosal melanoma is an aggressive melanoma subtype with poor response to antiprogrammed cell death-1 (PD-1) monotherapy. Axitinib in combination with toripalimab, a humanized IgG4 mAb against PD-1, showed a promising response rate in patients with metastatic mucosal melanoma (MM) in a phase Ib study. Here, we report the updated overall survival (OS), duration of response (DoR), and biomarker analysis results. METHODS: Patients with advanced MM received toripalimab 1 or 3 mg/kg intravenously every 2 weeks combined with axitinib 5 mg orally two times per day until disease progression or unacceptable toxicity. Tumor programmed cell death ligand-1 (PD-L1) expression, tumor mutational burden (TMB), and gene expression profile (GEP) by messenger RNA sequencing were evaluated for correlation with survival. RESULTS: As of April 2, 2021, the median follow-up was 42.5 months. Among 29 chemotherapy-naïve patients with metastatic MM, the median OS was 20.7 months (95% CI 9.7 to 32.7 months); the median progression-free survival (PFS) was 7.5 months (95% CI 3.8 to 14.8 months); and the median DoR was 13.4 months (95% CI 5.5 to 20.6 months). The OS rates of 1, 2, and 3 years were 62.1%, 44.8%, and 31.0%, respectively. Biomarker analysis found that PD-L1 expression and TMB level were not associated with survival benefits. In contrast, a 12-GEP signature correlated with improved PFS (17.7 vs 5.7 months, p=0.0083) and OS (35.6 vs 17.6 months, p=0.039). CONCLUSIONS: The 3-year survival update confirmed the antitumor activity and long-term survival benefit of the toripalimab plus axitinib combination in patients with advanced MM. The 12-gene GEP is of value in predicting the outcomes of vascular endothelial growth factor receptor-tyrosine kinase inhibitor and PD-1 blockade combination therapy, but requires further validation. TRIAL REGISTRATION NUMBERS: NCT03086174. BMJ Publishing Group 2022-02-21 /pmc/articles/PMC9066368/ /pubmed/35193932 http://dx.doi.org/10.1136/jitc-2021-004036 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
spellingShingle Clinical/Translational Cancer Immunotherapy
Li, Siming
Wu, Xiaowen
Yan, Xieqiao
Zhou, Li
Chi, Zhihong
Si, Lu
Cui, Chuanliang
Tang, Bixia
Mao, Lili
Lian, Bin
Wang, Xuan
Bai, Xue
Dai, Jie
Kong, Yan
Tang, Xiongwen
Feng, Hui
Yao, Sheng
Flaherty, Keith T
Guo, Jun
Sheng, Xinan
Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
title Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
title_full Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
title_fullStr Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
title_full_unstemmed Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
title_short Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
title_sort toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066368/
https://www.ncbi.nlm.nih.gov/pubmed/35193932
http://dx.doi.org/10.1136/jitc-2021-004036
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