Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical Case

Introduction. Cutaneous melanoma is a highly aggressive malignancy with a significant risk of metastasis. Current treatment strategies include surgical resection, immunotherapy, and targeted therapy directed at mutations in the MAPK/ ERK pathway, particularly BRAF V600E. Despite the efficacy of dual...

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Main Authors: V. E. Askarov, A. V. Sultanbaev, K. V. Menshikov, V. S. Chalov, N. I. Sultanbaeva, I. A. Menshikova
Format: Article
Language:English
Published: Bashkir State Medical University 2025-07-01
Series:Креативная хирургия и онкология
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Online Access:https://www.surgonco.ru/jour/article/view/1089
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author V. E. Askarov
A. V. Sultanbaev
K. V. Menshikov
V. S. Chalov
N. I. Sultanbaeva
I. A. Menshikova
author_facet V. E. Askarov
A. V. Sultanbaev
K. V. Menshikov
V. S. Chalov
N. I. Sultanbaeva
I. A. Menshikova
author_sort V. E. Askarov
collection DOAJ
description Introduction. Cutaneous melanoma is a highly aggressive malignancy with a significant risk of metastasis. Current treatment strategies include surgical resection, immunotherapy, and targeted therapy directed at mutations in the MAPK/ ERK pathway, particularly BRAF V600E. Despite the efficacy of dual BRAF/MEK inhibition, the rapid development of drug resistance remains a challenge, prompting interest in combination immunotherapy plus targeted therapy. Aim. This study aimed to evaluate the efficacy and tolerability of triple therapy, involving atezolizumab, vemurafenib, and cobimetinib in patients with BRAF V600 mutation-driven metastatic melanoma following failure of prior lines of therapy. Materials and methods. We present a detailed case report of a patient with metastatic cutaneous melanoma who achieved disease stabilization for 27 months following surgery and first-line therapy with dabrafenib and trametinib. After subsequent progression, second- and third-line therapies with pembrolizumab followed by pembrolizumab and lenvatinib were administered; however, both therapies proved ineffective. Fourth-line therapy with atezolizumab, vemurafenib, and cobimetinib demonstrated a significant clinical response. Results and discussion. Following six months of triple therapy, positron emission tomography/computed tomography (PET/CT) confirmed complete metabolic regression of the previously identified lesions, including those in the intrathoracic lymph nodes and pulmonary metastases. The treatment was well tolerated, with no grade 3–4 adverse events. Conclusion. This clinical case highlights the potential of the atezolizumab, vemurafenib, and cobimetinib therapy in patients with pretreated BRAF V600E-mutated metastatic melanoma. This regimen may benefit patients with acquired resistance to BRAF/MEK inhibitors and immune checkpoint inhibitors. The findings underscore the importance of personalized treatment strategies and the need for further research in this area.
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spelling doaj-art-a7ec6b496a9c4a208fb28e61d5e2821f2025-08-20T03:57:27ZengBashkir State Medical UniversityКреативная хирургия и онкология2076-30932307-05012025-07-0115217117810.24060/2076-3093-2025-15-2-75-82626Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical CaseV. E. Askarov0A. V. Sultanbaev1K. V. Menshikov2V. S. Chalov3N. I. Sultanbaeva4I. A. Menshikova5Republican Clinical Oncological DispensaryRepublican Clinical Oncological DispensaryRepublican Clinical Oncological Dispensary ; Bashkir State Medical UniversityNuclear Medicine CentreRepublican Clinical Oncological DispensaryBashkir State Medical UniversityIntroduction. Cutaneous melanoma is a highly aggressive malignancy with a significant risk of metastasis. Current treatment strategies include surgical resection, immunotherapy, and targeted therapy directed at mutations in the MAPK/ ERK pathway, particularly BRAF V600E. Despite the efficacy of dual BRAF/MEK inhibition, the rapid development of drug resistance remains a challenge, prompting interest in combination immunotherapy plus targeted therapy. Aim. This study aimed to evaluate the efficacy and tolerability of triple therapy, involving atezolizumab, vemurafenib, and cobimetinib in patients with BRAF V600 mutation-driven metastatic melanoma following failure of prior lines of therapy. Materials and methods. We present a detailed case report of a patient with metastatic cutaneous melanoma who achieved disease stabilization for 27 months following surgery and first-line therapy with dabrafenib and trametinib. After subsequent progression, second- and third-line therapies with pembrolizumab followed by pembrolizumab and lenvatinib were administered; however, both therapies proved ineffective. Fourth-line therapy with atezolizumab, vemurafenib, and cobimetinib demonstrated a significant clinical response. Results and discussion. Following six months of triple therapy, positron emission tomography/computed tomography (PET/CT) confirmed complete metabolic regression of the previously identified lesions, including those in the intrathoracic lymph nodes and pulmonary metastases. The treatment was well tolerated, with no grade 3–4 adverse events. Conclusion. This clinical case highlights the potential of the atezolizumab, vemurafenib, and cobimetinib therapy in patients with pretreated BRAF V600E-mutated metastatic melanoma. This regimen may benefit patients with acquired resistance to BRAF/MEK inhibitors and immune checkpoint inhibitors. The findings underscore the importance of personalized treatment strategies and the need for further research in this area.https://www.surgonco.ru/jour/article/view/1089melanomaatezolizumabvemurafenibcobimetinibimmunotherapytumor biomarkerssox transcription factorstargeted therapy
spellingShingle V. E. Askarov
A. V. Sultanbaev
K. V. Menshikov
V. S. Chalov
N. I. Sultanbaeva
I. A. Menshikova
Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical Case
Креативная хирургия и онкология
melanoma
atezolizumab
vemurafenib
cobimetinib
immunotherapy
tumor biomarkers
sox transcription factors
targeted therapy
title Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical Case
title_full Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical Case
title_fullStr Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical Case
title_full_unstemmed Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical Case
title_short Combination BRAF/MEK Inhibitor Targeted Therapy and Immunotherapy (atezolizumab + vemurafenib + cobimetinib) for Metastatic Cutaneous Melanoma: Clinical Case
title_sort combination braf mek inhibitor targeted therapy and immunotherapy atezolizumab vemurafenib cobimetinib for metastatic cutaneous melanoma clinical case
topic melanoma
atezolizumab
vemurafenib
cobimetinib
immunotherapy
tumor biomarkers
sox transcription factors
targeted therapy
url https://www.surgonco.ru/jour/article/view/1089
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