Melanoma, BRAF-mutated - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main BRAF-mutated melanoma page for regimens that include active anticancer treatment.
=Adjuvant therapy=
==Placebo==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Maio et al. 2018 (BRIM8) 	2012-2015 	Phase 3 (C)	Vemurafenib 	Did not meet primary endpoint of DFS1Median DFS: 15.4 vs 23.1 mo(HR 1.25, 95% CI 0.85-1.85)
Long et al. 2017 (COMBI-AD)	2013-01 to 2014-12 	Phase 3 (C)	Dabrafenib & Trametinib	Shorter RFS2 (primary endpoint)Median RFS: 16.6 vs 93.1 mo(HR 1.92, 95% CI 1.59-2.33)
1Reported efficacy is based on the results for cohort 2, which was analyzed first as per the prespecified approach.
2Reported efficacy for COMBI-AD is based on the 2020 update.
====Preceding treatment====
*BRIM8: Complete resection, timing not specified
*COMBI-AD: Completion lymphadenectomy, within 12 weeks
===References===
#COMBI-AD: Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, Larkin J, Nyakas M, Dutriaux C, Haydon A, Robert C, Mortier L, Schachter J, Schadendorf D, Lesimple T, Plummer R, Ji R, Zhang P, Mookerjee B, Legos J, Kefford R, Dummer R, Kirkwood JM. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017 Nov 9;377(19):1813-1823. Epub 2017 Sep 10. link to original article EuroPMC NCT01682083
##Update: Hauschild A, Dummer R, Schadendorf D, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, Larkin J, Nyakas M, Dutriaux C, Haydon A, Robert C, Mortier L, Schachter J, Lesimple T, Plummer R, Dasgupta K, Haas T, Shilkrut M, Gasal E, Kefford R, Kirkwood JM, Long GV. Longer Follow-Up Confirms Relapse-Free Survival Benefit With Adjuvant Dabrafenib Plus Trametinib in Patients With Resected BRAF V600-Mutant Stage III Melanoma. J Clin Oncol. 2018 Dec 10;36(35):3441-3449. Epub 2018 Oct 22. link to original article link to PMC article EuroPMC
## PRO analysis: Schadendorf D, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, Larkin J, Nyakas M, Dutriaux C, Haydon A, Robert C, Mortier L, Lesimple T, Plummer R, Schachter J, Dasgupta K, Manson S, Koruth R, Mookerjee B, Kefford R, Dummer R, Kirkwood JM, Long GV. Patient-reported outcomes in patients with resected, high-risk melanoma with BRAFV600E or BRAFV600K mutations treated with adjuvant dabrafenib plus trametinib (COMBI-AD): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 May;20(5):701-710. Epub 2019 Mar 27. link to original article EuroPMC
## Update: Dummer R, Hauschild A, Santinami M, Atkinson V, Mandalà M, Kirkwood JM, Chiarion Sileni V, Larkin J, Nyakas M, Dutriaux C, Haydon A, Robert C, Mortier L, Schachter J, Lesimple T, Plummer R, Dasgupta K, Gasal E, Tan M, Long GV, Schadendorf D. Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. N Engl J Med. 2020 Sep 17;383(12):1139-1148. Epub 2020 Sep 2. link to original article EuroPMC
##Update: Long GV, Hauschild A, Santinami M, Kirkwood JM, Atkinson V, Mandala M, Merelli B, Sileni VC, Nyakas M, Haydon A, Dutriaux C, Robert C, Mortier L, Schachter J, Schadendorf D, Lesimple T, Plummer R, Larkin J, Tan M, Adnaik SB, Burgess P, Jandoo T, Dummer R. Final Results for Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. N Engl J Med. 2024 Nov 7;391(18):1709-1720. Epub 2024 Jun 19. link to original article EuroPMC
#BRIM8: Maio M, Lewis K, Demidov L, Mandalà M, Bondarenko I, Ascierto PA, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Goodman GR, Simmons B, Ye C, Yan Y, Schadendorf D; BRIM8 Investigators. Adjuvant vemurafenib in resected, BRAF(V600) mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):510-520. Epub 2018 Feb 21. Erratum in: Lancet Oncol. 2018 Apr;19(4):e184. link to original article EuroPMC NCT01667419
##HRQoL analysis: Schadendorf D, Di Giacomo AM, Demidov L, Merelli B, Bondarenko I, Ascierto PA, Herbert C, Mackiewicz A, Rutkowski P, Guminski A, Goodman GR, Simmons B, Ye C, Hong A, Lewis K; BRIM8 Investigators. Health-related quality of life in patients with fully resected BRAFV600 mutation-positive melanoma receiving adjuvant vemurafenib. Eur J Cancer. 2019 Dec;123:155-161. Epub 2019 Nov 5. link to original article EuroPMC
Category:Melanoma regimens
Category:Null regimens
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