TY - JOUR
T1 - Efficacy, safety and factors associated with disease progression in patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma
T2 - An open label, non-randomized, phase IIIb study of trametinib in combination with dabrafenib
AU - Saiag, Philippe
AU - Robert, Caroline
AU - Grob, Jean Jacques
AU - Mortier, Laurent
AU - Dereure, Olivier
AU - Lebbe, Céleste
AU - Mansard, Sandrine
AU - Grange, Florent
AU - Neidhardt, Eve Marie
AU - Lesimple, Thierry
AU - Machet, Laurent
AU - Bedane, Christophe
AU - Maillard, Hervé
AU - Dalac-Rat, Sophie
AU - Nardin, Charlée
AU - Szenik, Alexandra
AU - Denden, Amine
AU - Dutriaux, Caroline
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Background: BRAF and MEK inhibitors combination, including dabrafenib (D) and trametinib (T) have transformed the treatment of BRAF V600-mutant advanced melanoma patients, including patients with brain metastasis (BM). In a large phase IIIb, single-arm, open-label, multicenter French study, we assessed safety, response to treatment, progression-free survival (PFS) and factors associated with progression, and stratified the population into risk groups. Methods: Patients with unresectable, advanced, BRAF V600-mutant melanoma were included, including those with the presence of BM, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2, elevated lactate dehydrogenase (LDH) or previous melanoma treatments. Responses were determined locally, without central review. PFS was estimated using the Kaplan–Meier analysis and modelled with multivariate Cox model. Risk subgroups were identified using a regression tree analysis. Results: Between March 2015 and November 2016, 856 patients received at least one D + T dose. Overall, 92% had stage IV melanoma, 38% ECOG PS ≥1, 32% BM and 37.5% elevated LDH. Median PFS was 8.02 months (95% confidence interval [CI] 7.33–8.77). Significant factors associated with lower PFS were ECOG PS ≥1, elevated LDH, ≥3 metastatic sites and presence of BM. Patients with <3 metastatic sites, ECOG = 0 and no BM had the highest probability of PFS at 6 months (83%, 95% CI 76–87) and 12 months (56%, 95% CI 47–64), respectively. Conclusions: This is the largest prospective study in advanced BRAF V600-mutant melanoma patients treated with D + T, conducted in conditions close to ‘real-world practice’. We confirm previous findings that LDH, ECOG PS and ≥3 metastatic sites are associated with shorter PFS, but the real-world setting introduces BM as a major prognostic factor.
AB - Background: BRAF and MEK inhibitors combination, including dabrafenib (D) and trametinib (T) have transformed the treatment of BRAF V600-mutant advanced melanoma patients, including patients with brain metastasis (BM). In a large phase IIIb, single-arm, open-label, multicenter French study, we assessed safety, response to treatment, progression-free survival (PFS) and factors associated with progression, and stratified the population into risk groups. Methods: Patients with unresectable, advanced, BRAF V600-mutant melanoma were included, including those with the presence of BM, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2, elevated lactate dehydrogenase (LDH) or previous melanoma treatments. Responses were determined locally, without central review. PFS was estimated using the Kaplan–Meier analysis and modelled with multivariate Cox model. Risk subgroups were identified using a regression tree analysis. Results: Between March 2015 and November 2016, 856 patients received at least one D + T dose. Overall, 92% had stage IV melanoma, 38% ECOG PS ≥1, 32% BM and 37.5% elevated LDH. Median PFS was 8.02 months (95% confidence interval [CI] 7.33–8.77). Significant factors associated with lower PFS were ECOG PS ≥1, elevated LDH, ≥3 metastatic sites and presence of BM. Patients with <3 metastatic sites, ECOG = 0 and no BM had the highest probability of PFS at 6 months (83%, 95% CI 76–87) and 12 months (56%, 95% CI 47–64), respectively. Conclusions: This is the largest prospective study in advanced BRAF V600-mutant melanoma patients treated with D + T, conducted in conditions close to ‘real-world practice’. We confirm previous findings that LDH, ECOG PS and ≥3 metastatic sites are associated with shorter PFS, but the real-world setting introduces BM as a major prognostic factor.
KW - BRAF V600-mutation
KW - Dabrafenib
KW - Melanoma
KW - Regression tree
KW - Trametinib
UR - http://www.scopus.com/inward/record.url?scp=85109192498&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.05.031
DO - 10.1016/j.ejca.2021.05.031
M3 - Article
C2 - 34243078
AN - SCOPUS:85109192498
SN - 0959-8049
VL - 154
SP - 57
EP - 65
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -