Cargando…

Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma

SIMPLE SUMMARY: Neoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery. 46 patients were treated with BRAFi/MEKi or BRAFi before surgery with 78% R0 resection. In patients with a maj...

Descripción completa

Detalles Bibliográficos
Autores principales: Czarnecka, Anna M., Ostaszewski, Krzysztof, Borkowska, Aneta, Szumera-Ciećkiewicz, Anna, Kozak, Katarzyna, Świtaj, Tomasz, Rogala, Paweł, Kalinowska, Iwona, Koseła-Paterczyk, Hanna, Zaborowski, Konrad, Teterycz, Paweł, Tysarowski, Andrzej, Makuła, Donata, Rutkowski, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744603/
https://www.ncbi.nlm.nih.gov/pubmed/35008274
http://dx.doi.org/10.3390/cancers14010110
_version_ 1784630145171062784
author Czarnecka, Anna M.
Ostaszewski, Krzysztof
Borkowska, Aneta
Szumera-Ciećkiewicz, Anna
Kozak, Katarzyna
Świtaj, Tomasz
Rogala, Paweł
Kalinowska, Iwona
Koseła-Paterczyk, Hanna
Zaborowski, Konrad
Teterycz, Paweł
Tysarowski, Andrzej
Makuła, Donata
Rutkowski, Piotr
author_facet Czarnecka, Anna M.
Ostaszewski, Krzysztof
Borkowska, Aneta
Szumera-Ciećkiewicz, Anna
Kozak, Katarzyna
Świtaj, Tomasz
Rogala, Paweł
Kalinowska, Iwona
Koseła-Paterczyk, Hanna
Zaborowski, Konrad
Teterycz, Paweł
Tysarowski, Andrzej
Makuła, Donata
Rutkowski, Piotr
author_sort Czarnecka, Anna M.
collection PubMed
description SIMPLE SUMMARY: Neoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery. 46 patients were treated with BRAFi/MEKi or BRAFi before surgery with 78% R0 resection. In patients with a major pathological response with no, or less than 10%, viable cells in the tumor, median DFS and PFS were significantly longer than in patients with a minor pathological response. ABSTRACT: 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.
format Online
Article
Text
id pubmed-8744603
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87446032022-01-11 Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma Czarnecka, Anna M. Ostaszewski, Krzysztof Borkowska, Aneta Szumera-Ciećkiewicz, Anna Kozak, Katarzyna Świtaj, Tomasz Rogala, Paweł Kalinowska, Iwona Koseła-Paterczyk, Hanna Zaborowski, Konrad Teterycz, Paweł Tysarowski, Andrzej Makuła, Donata Rutkowski, Piotr Cancers (Basel) Article SIMPLE SUMMARY: Neoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery. 46 patients were treated with BRAFi/MEKi or BRAFi before surgery with 78% R0 resection. In patients with a major pathological response with no, or less than 10%, viable cells in the tumor, median DFS and PFS were significantly longer than in patients with a minor pathological response. ABSTRACT: 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. MDPI 2021-12-27 /pmc/articles/PMC8744603/ /pubmed/35008274 http://dx.doi.org/10.3390/cancers14010110 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Czarnecka, Anna M.
Ostaszewski, Krzysztof
Borkowska, Aneta
Szumera-Ciećkiewicz, Anna
Kozak, Katarzyna
Świtaj, Tomasz
Rogala, Paweł
Kalinowska, Iwona
Koseła-Paterczyk, Hanna
Zaborowski, Konrad
Teterycz, Paweł
Tysarowski, Andrzej
Makuła, Donata
Rutkowski, Piotr
Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma
title Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma
title_full Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma
title_fullStr Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma
title_full_unstemmed Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma
title_short Efficacy of Neoadjuvant Targeted Therapy for Borderline Resectable III B-D or IV Stage BRAF (V600) Mutation-Positive Melanoma
title_sort efficacy of neoadjuvant targeted therapy for borderline resectable iii b-d or iv stage braf (v600) mutation-positive melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744603/
https://www.ncbi.nlm.nih.gov/pubmed/35008274
http://dx.doi.org/10.3390/cancers14010110
work_keys_str_mv AT czarneckaannam efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT ostaszewskikrzysztof efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT borkowskaaneta efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT szumeracieckiewiczanna efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT kozakkatarzyna efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT switajtomasz efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT rogalapaweł efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT kalinowskaiwona efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT kosełapaterczykhanna efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT zaborowskikonrad efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT teteryczpaweł efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT tysarowskiandrzej efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT makuładonata efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma
AT rutkowskipiotr efficacyofneoadjuvanttargetedtherapyforborderlineresectableiiibdorivstagebrafv600mutationpositivemelanoma