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Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials

BACKGROUND: We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) on ppOS. METHODS: Recursive partitioning analysis (RPA) was performed to model r...

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Autores principales: Ascierto, Paolo A., Ribas, Antoni, Larkin, James, McArthur, Grant A., Lewis, Karl D., Hauschild, Axel, Flaherty, Keith T., McKenna, Edward, Zhu, Qian, Mun, Yong, Dréno, Brigitte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397682/
https://www.ncbi.nlm.nih.gov/pubmed/32746839
http://dx.doi.org/10.1186/s12967-020-02458-x
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author Ascierto, Paolo A.
Ribas, Antoni
Larkin, James
McArthur, Grant A.
Lewis, Karl D.
Hauschild, Axel
Flaherty, Keith T.
McKenna, Edward
Zhu, Qian
Mun, Yong
Dréno, Brigitte
author_facet Ascierto, Paolo A.
Ribas, Antoni
Larkin, James
McArthur, Grant A.
Lewis, Karl D.
Hauschild, Axel
Flaherty, Keith T.
McKenna, Edward
Zhu, Qian
Mun, Yong
Dréno, Brigitte
author_sort Ascierto, Paolo A.
collection PubMed
description BACKGROUND: We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) on ppOS. METHODS: Recursive partitioning analysis (RPA) was performed to model relationships between prespecified covariates and ppOS in patients with BRAF(V600)-mutated metastatic melanoma who had experienced progressive disease (PD) following treatment with cobimetinib plus vemurafenib, vemurafenib monotherapy, or dacarbazine in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. Prognostic subgroups identified by RPA were then applied to pooled treatment cohorts. The primary endpoint was ppOS, defined as time from first PD to death from any cause. RESULTS: RPA identified baseline lactate dehydrogenase (LDH), baseline disease stage, Eastern Cooperative Oncology Group performance status at PD, and ppRx as significant prognostic factors for ppOS. Median ppOS was longest in patients with normal baseline LDH, stage M1c disease at baseline, and ppRx with immunotherapy or targeted therapy (12.2 months; 95% CI 10.3–16.1) and shortest in those with elevated baseline LDH > 2 × upper limit of normal (2.3 months; 95% CI 1.8–2.7). Original treatment assignment did not impact ppOS. Across treatment cohorts, patients treated with immunotherapy or targeted therapy after PD had better ppOS than those given other treatments. CONCLUSION: A combination of factors at baseline (LDH, disease stage) and PD (performance status, ppRx) impact ppOS outcomes. ppRx with immunotherapy or targeted therapy is an independent prognostic factor for improved overall survival following progression regardless of original treatment. Trial registration The trials included in this analysis are registered with ClinicalTrials.gov: NCT00949702 (BRIM-2), NCT01006980 (BRIM-3), NCT01271803 (BRIM-7), and NCT01689519 (coBRIM).
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spelling pubmed-73976822020-08-06 Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials Ascierto, Paolo A. Ribas, Antoni Larkin, James McArthur, Grant A. Lewis, Karl D. Hauschild, Axel Flaherty, Keith T. McKenna, Edward Zhu, Qian Mun, Yong Dréno, Brigitte J Transl Med Research BACKGROUND: We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) on ppOS. METHODS: Recursive partitioning analysis (RPA) was performed to model relationships between prespecified covariates and ppOS in patients with BRAF(V600)-mutated metastatic melanoma who had experienced progressive disease (PD) following treatment with cobimetinib plus vemurafenib, vemurafenib monotherapy, or dacarbazine in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. Prognostic subgroups identified by RPA were then applied to pooled treatment cohorts. The primary endpoint was ppOS, defined as time from first PD to death from any cause. RESULTS: RPA identified baseline lactate dehydrogenase (LDH), baseline disease stage, Eastern Cooperative Oncology Group performance status at PD, and ppRx as significant prognostic factors for ppOS. Median ppOS was longest in patients with normal baseline LDH, stage M1c disease at baseline, and ppRx with immunotherapy or targeted therapy (12.2 months; 95% CI 10.3–16.1) and shortest in those with elevated baseline LDH > 2 × upper limit of normal (2.3 months; 95% CI 1.8–2.7). Original treatment assignment did not impact ppOS. Across treatment cohorts, patients treated with immunotherapy or targeted therapy after PD had better ppOS than those given other treatments. CONCLUSION: A combination of factors at baseline (LDH, disease stage) and PD (performance status, ppRx) impact ppOS outcomes. ppRx with immunotherapy or targeted therapy is an independent prognostic factor for improved overall survival following progression regardless of original treatment. Trial registration The trials included in this analysis are registered with ClinicalTrials.gov: NCT00949702 (BRIM-2), NCT01006980 (BRIM-3), NCT01271803 (BRIM-7), and NCT01689519 (coBRIM). BioMed Central 2020-08-03 /pmc/articles/PMC7397682/ /pubmed/32746839 http://dx.doi.org/10.1186/s12967-020-02458-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ascierto, Paolo A.
Ribas, Antoni
Larkin, James
McArthur, Grant A.
Lewis, Karl D.
Hauschild, Axel
Flaherty, Keith T.
McKenna, Edward
Zhu, Qian
Mun, Yong
Dréno, Brigitte
Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
title Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
title_full Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
title_fullStr Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
title_full_unstemmed Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
title_short Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
title_sort impact of initial treatment and prognostic factors on postprogression survival in braf-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397682/
https://www.ncbi.nlm.nih.gov/pubmed/32746839
http://dx.doi.org/10.1186/s12967-020-02458-x
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