Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive Melanoma
Neoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery and adjuvant treatment as it is for sarcoma, breast, rectal, esophageal, or gastric cancers. Patients with locoregional recurre...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/1/110 |
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| author | Anna M. Czarnecka Krzysztof Ostaszewski Aneta Borkowska Anna Szumera-Ciećkiewicz Katarzyna Kozak Tomasz Świtaj Paweł Rogala Iwona Kalinowska Hanna Koseła-Paterczyk Konrad Zaborowski Paweł Teterycz Andrzej Tysarowski Donata Makuła Piotr Rutkowski |
| author_facet | Anna M. Czarnecka Krzysztof Ostaszewski Aneta Borkowska Anna Szumera-Ciećkiewicz Katarzyna Kozak Tomasz Świtaj Paweł Rogala Iwona Kalinowska Hanna Koseła-Paterczyk Konrad Zaborowski Paweł Teterycz Andrzej Tysarowski Donata Makuła Piotr Rutkowski |
| author_sort | Anna M. Czarnecka |
| collection | DOAJ |
| description | Neoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery and adjuvant treatment as it is for sarcoma, breast, rectal, esophageal, or gastric cancers. Patients with locoregional recurrence after initial surgery and those with advanced regional lymphatic metastases are at a high risk of relapse and melanoma-related death. There is an unmet clinical need to improve the outcomes for such patients. Patients with resectable bulky stage III or resectable stage IV histologically confirmed melanoma were enrolled and received standard-dose BRAFi/MEKi for at least 12 weeks before feasible resection of the pre-therapy target and then received at least for the next 40 weeks further BRAFi/MEKi. Of these patients, 37 were treated with dabrafenib and trametinib, three were treated with vemurafenib and cobimetinib, five with vemurafenib, and one with dabrafenib alone. All patients underwent surgery with 78% microscopically margin-negative resection (R0) resection. Ten patients achieved a complete pathological response. In patients with a major pathological response with no, or less than 10%, viable cells in the tumor, median disease free survival and progression free survival were significantly longer than in patients with a minor pathological response. No patient discontinued neoadjuvant BRAFi/MEKi due to toxicity. BRAFi/MEKi pre-treatment did not result in any new specific complications of surgery. Fourteen patients experienced disease recurrence or progression during post-operative treatment. We confirmed that BRAFi/MEKi combination is an effective and safe regimen in the perioperative treatment of melanoma. Pathological response to neoadjuvant treatment may be considered as a surrogate biomarker of disease recurrence. |
| first_indexed | 2024-03-10T03:47:09Z |
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| id | doaj.art-3ed327f18d424e339b5dbd8111b56f7c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T03:47:09Z |
| publishDate | 2021-12-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3ed327f18d424e339b5dbd8111b56f7c2023-11-23T11:16:13ZengMDPI AGCancers2072-66942021-12-0114111010.3390/cancers14010110Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive MelanomaAnna M. Czarnecka0Krzysztof Ostaszewski1Aneta Borkowska2Anna Szumera-Ciećkiewicz3Katarzyna Kozak4Tomasz Świtaj5Paweł Rogala6Iwona Kalinowska7Hanna Koseła-Paterczyk8Konrad Zaborowski9Paweł Teterycz10Andrzej Tysarowski11Donata Makuła12Piotr Rutkowski13Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Pathology and Laboratory Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Pathology and Laboratory Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Radiology I, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandNeoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery and adjuvant treatment as it is for sarcoma, breast, rectal, esophageal, or gastric cancers. Patients with locoregional recurrence after initial surgery and those with advanced regional lymphatic metastases are at a high risk of relapse and melanoma-related death. There is an unmet clinical need to improve the outcomes for such patients. Patients with resectable bulky stage III or resectable stage IV histologically confirmed melanoma were enrolled and received standard-dose BRAFi/MEKi for at least 12 weeks before feasible resection of the pre-therapy target and then received at least for the next 40 weeks further BRAFi/MEKi. Of these patients, 37 were treated with dabrafenib and trametinib, three were treated with vemurafenib and cobimetinib, five with vemurafenib, and one with dabrafenib alone. All patients underwent surgery with 78% microscopically margin-negative resection (R0) resection. Ten patients achieved a complete pathological response. In patients with a major pathological response with no, or less than 10%, viable cells in the tumor, median disease free survival and progression free survival were significantly longer than in patients with a minor pathological response. No patient discontinued neoadjuvant BRAFi/MEKi due to toxicity. BRAFi/MEKi pre-treatment did not result in any new specific complications of surgery. Fourteen patients experienced disease recurrence or progression during post-operative treatment. We confirmed that BRAFi/MEKi combination is an effective and safe regimen in the perioperative treatment of melanoma. Pathological response to neoadjuvant treatment may be considered as a surrogate biomarker of disease recurrence.https://www.mdpi.com/2072-6694/14/1/110melanomaneoadjuvantBRAFtargeted therapy |
| spellingShingle | Anna M. Czarnecka Krzysztof Ostaszewski Aneta Borkowska Anna Szumera-Ciećkiewicz Katarzyna Kozak Tomasz Świtaj Paweł Rogala Iwona Kalinowska Hanna Koseła-Paterczyk Konrad Zaborowski Paweł Teterycz Andrzej Tysarowski Donata Makuła Piotr Rutkowski Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive Melanoma Cancers melanoma neoadjuvant BRAF targeted therapy |
| title | Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive Melanoma |
| title_full | Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive Melanoma |
| title_fullStr | Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive Melanoma |
| title_full_unstemmed | Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive Melanoma |
| title_short | Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF <sup>V600</sup> Mutation-Positive Melanoma |
| title_sort | efficacy of neoadjuvant targeted therapy for borderline resectable iii b d or iv stage braf sup v600 sup mutation positive melanoma |
| topic | melanoma neoadjuvant BRAF targeted therapy |
| url | https://www.mdpi.com/2072-6694/14/1/110 |
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