The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis
Objectives: Immune-checkpoint inhibitors (ICI) and targeted-therapies (TT) have become standard options for BRAF-V600 metastatic melanomas (MM). Recently, randomized trials (RCT) addressed the efficacy of combined approaches, with conflicting results. We sought to evaluate efficacy and safety of fir...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Sociedade Brasileira de Oncologia Clínica, Sociedade Brasileira de Cirurgia Clínica and Sociedade Brasileira de Radioterapia
2022-10-01
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| Series: | Brazilian Journal of Oncology |
| Subjects: | |
| Online Access: | https://www.brazilianjournalofoncology.com.br/details/189/en-US/the-addition-of-pd-1-pd-l1-axis-blockade-to-braf-and-mek-inhibition-for-advanced-melanoma-patients-harboring-braf-mutations--a-systematic-review-and-m |
| _version_ | 1797673886923358208 |
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| author | Mauricio Fernando Silva Almeida Ribeiro Camila Bragança Xavier Allan Andresson Lima Pereira Mariana Scaranti Luiza Dib Batista Bugiato Faria Tatiana Strava Correa Marina Sahade David Queiroz Borges Muniz Olavo Feher Gustavo dos Santos Fernandes Artur Katz Rodrigo Ramella Munhoz |
| author_facet | Mauricio Fernando Silva Almeida Ribeiro Camila Bragança Xavier Allan Andresson Lima Pereira Mariana Scaranti Luiza Dib Batista Bugiato Faria Tatiana Strava Correa Marina Sahade David Queiroz Borges Muniz Olavo Feher Gustavo dos Santos Fernandes Artur Katz Rodrigo Ramella Munhoz |
| author_sort | Mauricio Fernando Silva Almeida Ribeiro |
| collection | DOAJ |
| description | Objectives: Immune-checkpoint inhibitors (ICI) and targeted-therapies (TT) have become standard options for BRAF-V600 metastatic melanomas (MM). Recently, randomized trials (RCT) addressed the efficacy of combined approaches, with conflicting results. We sought to evaluate efficacy and safety of first-line combination ICI and BRAF/MEK inhibitors (triplets) versus BRAF/MEKi (doublets).
Methods: We performed a systematic review and metaanalysis of RCT comparing triplet versus doublet published in MEDLINE and EMBASE from 2016-September/2020. We obtained pooled effect estimates through random-effects model assuming p<0.05 as statistically significant.
Results: Among 1,784 studies, 3 RCT were selected. Triplets demonstrated progression-free survival (PFS) (HR 0.79 - CI 0.68-0.91, p=0.001) and overall survival (OS) improvement (HR 0.81 - CI 0.67-0.98, p=0.03), with increased rates of grades 3/4 adverse events (AEs), any grade pyrexia, arthralgia, and aminotransferases elevation. AEdiscontinuation rates of all drugs remained similar.
Conclusions: Triplets improved PFS and OS with manageable toxicities. These are preliminary results and mature data are expected. |
| first_indexed | 2024-03-11T21:51:53Z |
| format | Article |
| id | doaj.art-d8baab6b1db4491c84f2d3e64dbf6379 |
| institution | Directory Open Access Journal |
| issn | 2526-8732 |
| language | English |
| last_indexed | 2024-03-11T21:51:53Z |
| publishDate | 2022-10-01 |
| publisher | Sociedade Brasileira de Oncologia Clínica, Sociedade Brasileira de Cirurgia Clínica and Sociedade Brasileira de Radioterapia |
| record_format | Article |
| series | Brazilian Journal of Oncology |
| spelling | doaj.art-d8baab6b1db4491c84f2d3e64dbf63792023-09-26T09:00:21ZengSociedade Brasileira de Oncologia Clínica, Sociedade Brasileira de Cirurgia Clínica and Sociedade Brasileira de RadioterapiaBrazilian Journal of Oncology2526-87322022-10-01180010.5935/2526-8732.20220298The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysisMauricio Fernando Silva Almeida Ribeiro0https://orcid.org/0000-0002-5602-164XCamila Bragança Xavier1Allan Andresson Lima Pereira2Mariana Scaranti3Luiza Dib Batista Bugiato Faria4Tatiana Strava Correa5Marina Sahade6David Queiroz Borges Muniz7Olavo Feher8Gustavo dos Santos Fernandes9Artur Katz10Rodrigo Ramella Munhoz11Hospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilHospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilHospital Sírio-Libanês, Oncology Center - Brasília - DF - BrazilHospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilHospital Sírio-Libanês, Oncology Center - Brasília - DF - BrazilHospital Sírio-Libanês, Oncology Center - Brasília - DF - BrazilHospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilHospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilHospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilHospital Sírio-Libanês, Oncology Center - Brasília - DF - BrazilHospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilHospital Sírio-Libanês, Oncology Center - Sao Paulo - SP - BrazilObjectives: Immune-checkpoint inhibitors (ICI) and targeted-therapies (TT) have become standard options for BRAF-V600 metastatic melanomas (MM). Recently, randomized trials (RCT) addressed the efficacy of combined approaches, with conflicting results. We sought to evaluate efficacy and safety of first-line combination ICI and BRAF/MEK inhibitors (triplets) versus BRAF/MEKi (doublets). Methods: We performed a systematic review and metaanalysis of RCT comparing triplet versus doublet published in MEDLINE and EMBASE from 2016-September/2020. We obtained pooled effect estimates through random-effects model assuming p<0.05 as statistically significant. Results: Among 1,784 studies, 3 RCT were selected. Triplets demonstrated progression-free survival (PFS) (HR 0.79 - CI 0.68-0.91, p=0.001) and overall survival (OS) improvement (HR 0.81 - CI 0.67-0.98, p=0.03), with increased rates of grades 3/4 adverse events (AEs), any grade pyrexia, arthralgia, and aminotransferases elevation. AEdiscontinuation rates of all drugs remained similar. Conclusions: Triplets improved PFS and OS with manageable toxicities. These are preliminary results and mature data are expected.https://www.brazilianjournalofoncology.com.br/details/189/en-US/the-addition-of-pd-1-pd-l1-axis-blockade-to-braf-and-mek-inhibition-for-advanced-melanoma-patients-harboring-braf-mutations--a-systematic-review-and-mmelanomaprogrammed cell death 1 receptorproto-oncogene proteins b-rafmap kinase signaling systemimmunotherapy |
| spellingShingle | Mauricio Fernando Silva Almeida Ribeiro Camila Bragança Xavier Allan Andresson Lima Pereira Mariana Scaranti Luiza Dib Batista Bugiato Faria Tatiana Strava Correa Marina Sahade David Queiroz Borges Muniz Olavo Feher Gustavo dos Santos Fernandes Artur Katz Rodrigo Ramella Munhoz The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis Brazilian Journal of Oncology melanoma programmed cell death 1 receptor proto-oncogene proteins b-raf map kinase signaling system immunotherapy |
| title | The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis |
| title_full | The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis |
| title_fullStr | The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis |
| title_full_unstemmed | The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis |
| title_short | The addition of PD-1/PD-L1 axis blockade to BRAF and MEK inhibition for advanced melanoma patients harboring BRAF mutations: a systematic review and meta-analysis |
| title_sort | addition of pd 1 pd l1 axis blockade to braf and mek inhibition for advanced melanoma patients harboring braf mutations a systematic review and meta analysis |
| topic | melanoma programmed cell death 1 receptor proto-oncogene proteins b-raf map kinase signaling system immunotherapy |
| url | https://www.brazilianjournalofoncology.com.br/details/189/en-US/the-addition-of-pd-1-pd-l1-axis-blockade-to-braf-and-mek-inhibition-for-advanced-melanoma-patients-harboring-braf-mutations--a-systematic-review-and-m |
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