Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib

Georgina V. Long, Zeynep Eroglu, Jeffrey Infante, Sapna Patel, Adil Daud, Douglas B. Johnson, Rene Gonzalez, Richard Kefford, Omid Hamid, Lynn Schuchter, Jonathan Cebon, William Sharfman, Robert McWilliams, Mario Sznol, Suman Redhu, Eduard Gasal, Bijoyesh Mookerjee, Jeffrey Weber, Keith T. Flaherty

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Abstract

Purpose: To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods: BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1: 1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results: As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion: This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.

LanguageEnglish
Pages667-673
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number7
DOIs
Publication statusPublished - 1 Mar 2018

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Melanoma
Mitogen-Activated Protein Kinase Kinases
Safety
Disease-Free Survival
dabrafenib
trametinib
L-Lactate Dehydrogenase
Therapeutics
Neoplasm Metastasis
Survival

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Long, Georgina V. ; Eroglu, Zeynep ; Infante, Jeffrey ; Patel, Sapna ; Daud, Adil ; Johnson, Douglas B. ; Gonzalez, Rene ; Kefford, Richard ; Hamid, Omid ; Schuchter, Lynn ; Cebon, Jonathan ; Sharfman, William ; McWilliams, Robert ; Sznol, Mario ; Redhu, Suman ; Gasal, Eduard ; Mookerjee, Bijoyesh ; Weber, Jeffrey ; Flaherty, Keith T. / Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 7. pp. 667-673.
@article{af49f92b265847e596d32e5ab3c6b485,
title = "Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib",
abstract = "Purpose: To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods: BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1: 1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results: As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24{\%}] of 54 enrolled at this dose plus five [11{\%}] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30{\%}; 5 years, 28{\%}) and progression-free survival (4 and 5 years, both 13{\%}) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45{\%}) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51{\%}). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion: This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.",
author = "Long, {Georgina V.} and Zeynep Eroglu and Jeffrey Infante and Sapna Patel and Adil Daud and Johnson, {Douglas B.} and Rene Gonzalez and Richard Kefford and Omid Hamid and Lynn Schuchter and Jonathan Cebon and William Sharfman and Robert McWilliams and Mario Sznol and Suman Redhu and Eduard Gasal and Bijoyesh Mookerjee and Jeffrey Weber and Flaherty, {Keith T.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1200/JCO.2017.74.1025",
language = "English",
volume = "36",
pages = "667--673",
journal = "Journal of Clinical Oncology",
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publisher = "American Society of Clinical Oncology",
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Long, GV, Eroglu, Z, Infante, J, Patel, S, Daud, A, Johnson, DB, Gonzalez, R, Kefford, R, Hamid, O, Schuchter, L, Cebon, J, Sharfman, W, McWilliams, R, Sznol, M, Redhu, S, Gasal, E, Mookerjee, B, Weber, J & Flaherty, KT 2018, 'Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib', Journal of Clinical Oncology, vol. 36, no. 7, pp. 667-673. https://doi.org/10.1200/JCO.2017.74.1025

Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib. / Long, Georgina V.; Eroglu, Zeynep; Infante, Jeffrey; Patel, Sapna; Daud, Adil; Johnson, Douglas B.; Gonzalez, Rene; Kefford, Richard; Hamid, Omid; Schuchter, Lynn; Cebon, Jonathan; Sharfman, William; McWilliams, Robert; Sznol, Mario; Redhu, Suman; Gasal, Eduard; Mookerjee, Bijoyesh; Weber, Jeffrey; Flaherty, Keith T.

In: Journal of Clinical Oncology, Vol. 36, No. 7, 01.03.2018, p. 667-673.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma who received dabrafenib combined with trametinib

AU - Long, Georgina V.

AU - Eroglu, Zeynep

AU - Infante, Jeffrey

AU - Patel, Sapna

AU - Daud, Adil

AU - Johnson, Douglas B.

AU - Gonzalez, Rene

AU - Kefford, Richard

AU - Hamid, Omid

AU - Schuchter, Lynn

AU - Cebon, Jonathan

AU - Sharfman, William

AU - McWilliams, Robert

AU - Sznol, Mario

AU - Redhu, Suman

AU - Gasal, Eduard

AU - Mookerjee, Bijoyesh

AU - Weber, Jeffrey

AU - Flaherty, Keith T.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Purpose: To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods: BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1: 1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results: As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion: This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.

AB - Purpose: To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods: BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1: 1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results: As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion: This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.

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U2 - 10.1200/JCO.2017.74.1025

DO - 10.1200/JCO.2017.74.1025

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EP - 673

JO - Journal of Clinical Oncology

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JF - Journal of Clinical Oncology

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