Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysis
Abstract Background Atezolizumab plus bevacizumab has shown promising efficacy in advanced mucosal melanoma in the multi‐centre phase II study. This report updates 3‐year survival outcomes and multi‐omics analysis to identify potential response biomarkers. Methods Forty‐three intention‐to‐treat (ITT...
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2025-01-01
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| Online Access: | https://doi.org/10.1002/ctm2.70169 |
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| author | Jie Dai Tianxiao Xu Lifeng Li Meiyu Fang Jing Lin Jun Cao Xue Bai Caili Li Xiaoting Wei Junjie Gu Yaoyao Liu Xuan Gao Xuefeng Xia Jun Guo Yu Chen Lili Mao Lu Si |
| author_facet | Jie Dai Tianxiao Xu Lifeng Li Meiyu Fang Jing Lin Jun Cao Xue Bai Caili Li Xiaoting Wei Junjie Gu Yaoyao Liu Xuan Gao Xuefeng Xia Jun Guo Yu Chen Lili Mao Lu Si |
| author_sort | Jie Dai |
| collection | DOAJ |
| description | Abstract Background Atezolizumab plus bevacizumab has shown promising efficacy in advanced mucosal melanoma in the multi‐centre phase II study. This report updates 3‐year survival outcomes and multi‐omics analysis to identify potential response biomarkers. Methods Forty‐three intention‐to‐treat (ITT) patients received intravenous administration of atezolizumab and bevacizumab every 3 weeks. Available samples underwent whole exome sequencing, transcriptome sequencing and targeted bisulphite sequencing to assess correlations with clinical outcomes. Results With a median follow‐up of 40.3 months, the median overall survival (mOS) was 23.7 months (95% confidence interval [CI], 15.1–34), and the 3‐year OS rate was 28.7% (95% CI, 17.6%–46.8%). Patients with upper site melanoma exhibited longer progression‐free survival (PFS), higher tumour neoantigen burden (TNB) and greater copy number variations (CNVs) burden compared to those with lower site melanoma. NRAS mutations were associated with enhanced angiogenesis, with five of six patients achieving partial response. Inflammatory cell infiltration, angiogenic status and activation of the SMAD2 and p38 MAPK pathways may be prognostic indicators. Conclusions This 3‐year updated analysis confirms the sustained efficacy of atezolizumab in combination of bevacizumab in patients with advanced mucosal melanoma. Inflammatory cell infiltration and angiogenic status were associated with therapeutic response. Furthermore, mucosal melanoma of upper site and NRAS mutation appear to be good predictors of response to immune checkpoint inhibitor and anti‐angiogenic combination treatment. Targeting SMAD2 and p38 MAPK pathways may further improve the outcome of mucosal melanoma. Key points 3‐year follow‐up study confirmed the therapeutic efficacy of atezolizumab combined with bevacizumab Tumors in the upper site and NRAS mutations are more sensitive to treatment Inflammatory cell infiltration, angiogenic status, and activation of the SMAD2 and p38 MAPK pathways may be prognostic indicators |
| format | Article |
| id | doaj-art-b2929b4655e742f1a452703bb233ea97 |
| institution | Kabale University |
| issn | 2001-1326 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj-art-b2929b4655e742f1a452703bb233ea972025-01-25T04:00:38ZengWileyClinical and Translational Medicine2001-13262025-01-01151n/an/a10.1002/ctm2.70169Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysisJie Dai0Tianxiao Xu1Lifeng Li2Meiyu Fang3Jing Lin4Jun Cao5Xue Bai6Caili Li7Xiaoting Wei8Junjie Gu9Yaoyao Liu10Xuan Gao11Xuefeng Xia12Jun Guo13Yu Chen14Lili Mao15Lu Si16Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaGeneplus‐Beijing Beijing ChinaDepartment of Rare Cancer & Head and Neck Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences, Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province Hangzhou ChinaDepartment of Medical Oncology Fujian Cancer Hospital & Fujian Medical University Cancer Hospital Fujian ChinaDepartment of Rare Cancer & Head and Neck Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences, Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province Hangzhou ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaGeneplus‐Beijing Beijing ChinaGeneplus‐Beijing Beijing ChinaGeneplus‐Beijing Beijing ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaDepartment of Medical Oncology Fujian Cancer Hospital & Fujian Medical University Cancer Hospital Fujian ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma Peking University Cancer Hospital and Institute Beijing ChinaAbstract Background Atezolizumab plus bevacizumab has shown promising efficacy in advanced mucosal melanoma in the multi‐centre phase II study. This report updates 3‐year survival outcomes and multi‐omics analysis to identify potential response biomarkers. Methods Forty‐three intention‐to‐treat (ITT) patients received intravenous administration of atezolizumab and bevacizumab every 3 weeks. Available samples underwent whole exome sequencing, transcriptome sequencing and targeted bisulphite sequencing to assess correlations with clinical outcomes. Results With a median follow‐up of 40.3 months, the median overall survival (mOS) was 23.7 months (95% confidence interval [CI], 15.1–34), and the 3‐year OS rate was 28.7% (95% CI, 17.6%–46.8%). Patients with upper site melanoma exhibited longer progression‐free survival (PFS), higher tumour neoantigen burden (TNB) and greater copy number variations (CNVs) burden compared to those with lower site melanoma. NRAS mutations were associated with enhanced angiogenesis, with five of six patients achieving partial response. Inflammatory cell infiltration, angiogenic status and activation of the SMAD2 and p38 MAPK pathways may be prognostic indicators. Conclusions This 3‐year updated analysis confirms the sustained efficacy of atezolizumab in combination of bevacizumab in patients with advanced mucosal melanoma. Inflammatory cell infiltration and angiogenic status were associated with therapeutic response. Furthermore, mucosal melanoma of upper site and NRAS mutation appear to be good predictors of response to immune checkpoint inhibitor and anti‐angiogenic combination treatment. Targeting SMAD2 and p38 MAPK pathways may further improve the outcome of mucosal melanoma. Key points 3‐year follow‐up study confirmed the therapeutic efficacy of atezolizumab combined with bevacizumab Tumors in the upper site and NRAS mutations are more sensitive to treatment Inflammatory cell infiltration, angiogenic status, and activation of the SMAD2 and p38 MAPK pathways may be prognostic indicatorshttps://doi.org/10.1002/ctm2.70169atezolizumabbevacizumabimmunotherapymucosal melanomaVEGF inhibitor |
| spellingShingle | Jie Dai Tianxiao Xu Lifeng Li Meiyu Fang Jing Lin Jun Cao Xue Bai Caili Li Xiaoting Wei Junjie Gu Yaoyao Liu Xuan Gao Xuefeng Xia Jun Guo Yu Chen Lili Mao Lu Si Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysis Clinical and Translational Medicine atezolizumab bevacizumab immunotherapy mucosal melanoma VEGF inhibitor |
| title | Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysis |
| title_full | Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysis |
| title_fullStr | Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysis |
| title_full_unstemmed | Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysis |
| title_short | Atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma: 3‐year survival update and multi‐omics analysis |
| title_sort | atezolizumab plus bevacizumab in patients with unresectable or metastatic mucosal melanoma 3 year survival update and multi omics analysis |
| topic | atezolizumab bevacizumab immunotherapy mucosal melanoma VEGF inhibitor |
| url | https://doi.org/10.1002/ctm2.70169 |
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