TY - JOUR
T1 - Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma
AU - Robert, C.
AU - Grob, J. J.
AU - Stroyakovskiy, D.
AU - Karaszewska, B.
AU - Hauschild, A.
AU - Levchenko, E.
AU - Chiarion Sileni, V.
AU - Schachter, J.
AU - Garbe, C.
AU - Bondarenko, I.
AU - Gogas, H.
AU - Mandalá, M.
AU - Haanen, J. B.A.G.
AU - Lebbé, C.
AU - MacKiewicz, A.
AU - Rutkowski, P.
AU - Nathan, P. D.
AU - Ribas, A.
AU - Davies, M. A.
AU - Flaherty, K. T.
AU - Burgess, P.
AU - Tan, M.
AU - Gasal, E.
AU - Voi, M.
AU - Schadendorf, D.
AU - Long, G. V.
N1 - Publisher Copyright:
© 2019 Massachusetts Medical Society.
PY - 2019/8/15
Y1 - 2019/8/15
N2 - BACKGROUND Patients who have unresectable or metastatic melanoma with a BRAF V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors. METHODS We analyzed pooled extended-survival data from two trials involving previously untreated patients who had received BRAF inhibitor dabrafenib (at a dose of 150 mg twice daily) plus MEK inhibitor trametinib (2 mg once daily) in the COMBI-d and COMBI-v trials. The median duration of follow-up was 22 months (range, 0 to 76). The primary end points in the COMBI-d and COMBI-v trials were progression-free survival and overall survival, respectively. RESULTS A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The progressionfree survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several baseline factors (e.g., performance status, age, sex, number of organ sites with metastasis, and lactate dehydrogenase level) were significantly associated with both progression-free survival and overall survival. A complete response occurred in 109 patients (19%) and was associated with an improved long-term outcome, with an overall survival rate of 71% (95% CI, 62 to 79) at 5 years. CONCLUSIONS First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.
AB - BACKGROUND Patients who have unresectable or metastatic melanoma with a BRAF V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors. METHODS We analyzed pooled extended-survival data from two trials involving previously untreated patients who had received BRAF inhibitor dabrafenib (at a dose of 150 mg twice daily) plus MEK inhibitor trametinib (2 mg once daily) in the COMBI-d and COMBI-v trials. The median duration of follow-up was 22 months (range, 0 to 76). The primary end points in the COMBI-d and COMBI-v trials were progression-free survival and overall survival, respectively. RESULTS A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The progressionfree survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several baseline factors (e.g., performance status, age, sex, number of organ sites with metastasis, and lactate dehydrogenase level) were significantly associated with both progression-free survival and overall survival. A complete response occurred in 109 patients (19%) and was associated with an improved long-term outcome, with an overall survival rate of 71% (95% CI, 62 to 79) at 5 years. CONCLUSIONS First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.
UR - http://www.scopus.com/inward/record.url?scp=85069667308&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069667308&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1904059
DO - 10.1056/NEJMoa1904059
M3 - Article
C2 - 31166680
AN - SCOPUS:85069667308
SN - 0028-4793
VL - 381
SP - 626
EP - 636
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 7
ER -