TY - JOUR
T1 - Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study
AU - Valpione, S.
AU - Carlino, M S
AU - Mangana, Johanna
AU - Mooradian, Meghan J
AU - McArthur, G
AU - Schadendorf, Dirk
AU - Hauschild, Axel
AU - Menzies, Alexander M
AU - Arance, Ana
AU - Ascierto, Paolo
AU - Di Giacomo, AnnaMaria
AU - de Rosa, Francesco
AU - Larkin, James
AU - Park, John J
AU - Goldinger, S M
AU - Sullivan, Ryan J
AU - Xu, Wen
AU - Livingstone , Elisabeth
AU - Weichenthal, Michael
AU - Rai, Rajat
AU - Gaba, Lydia
AU - Long, Georgina V.
AU - Lorigan, Paul
N1 - EJC 91(2018)116-124
PY - 2018/3
Y1 - 2018/3
N2 - Background
Most metastatic melanoma patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with acquired resistance due to genetic changes, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse retrospectively outcomes for patients retreated with BRAF directed therapy.
Patients and Methods
116 metastatic melanoma patients who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi at 14 centres in Europe, US and Australia were studied respectively. Response rate (RR), overall survival (OS) and progression free survival (PFS) from the start of retreatment were calculated.
Results
The median duration of treatment was 9.4 months for first BRAFi +/- MEKi treatment and 7.7 months for the subsequent treatment (immunotherapy 72%, other 17 %, drug holiday 11%) after BRAFi discontinuation. Brain metastases were present in 51 (44%) patients at BRAFi retreatment. The RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease (SD) 24% and progressive disease (PD) 30%, 4% missing. Of 83 patients who previously discontinued BRAFi due to disease progression, 31 (37.3%) responded (30 PR and 1 CR) to retreatment. The median OS from retreatment was 9.8 months and PFS was 5 months. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR=1.32 for each additional organ with metastases, p<.001), LDH (HR=1.37 for each multiple of the upper normal limit, p<.001), while re-challenge with combination BRAFi+MEKi conferred a better OS vs BRAFi alone (HR=0.5, P=.006).
Conclusion
Re-challenge with BRAFi +/- MEKi results in a clinically meaningful benefit and should be considered for selected patients.
AB - Background
Most metastatic melanoma patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with acquired resistance due to genetic changes, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse retrospectively outcomes for patients retreated with BRAF directed therapy.
Patients and Methods
116 metastatic melanoma patients who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi at 14 centres in Europe, US and Australia were studied respectively. Response rate (RR), overall survival (OS) and progression free survival (PFS) from the start of retreatment were calculated.
Results
The median duration of treatment was 9.4 months for first BRAFi +/- MEKi treatment and 7.7 months for the subsequent treatment (immunotherapy 72%, other 17 %, drug holiday 11%) after BRAFi discontinuation. Brain metastases were present in 51 (44%) patients at BRAFi retreatment. The RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease (SD) 24% and progressive disease (PD) 30%, 4% missing. Of 83 patients who previously discontinued BRAFi due to disease progression, 31 (37.3%) responded (30 PR and 1 CR) to retreatment. The median OS from retreatment was 9.8 months and PFS was 5 months. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR=1.32 for each additional organ with metastases, p<.001), LDH (HR=1.37 for each multiple of the upper normal limit, p<.001), while re-challenge with combination BRAFi+MEKi conferred a better OS vs BRAFi alone (HR=0.5, P=.006).
Conclusion
Re-challenge with BRAFi +/- MEKi results in a clinically meaningful benefit and should be considered for selected patients.
UR - https://www.scopus.com/pages/publications/85040702752
U2 - 10.1016/j.ejca.2017.12.007
DO - 10.1016/j.ejca.2017.12.007
M3 - Article
SN - 0959-8049
VL - 91
SP - 116
EP - 124
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -
