TY - JOUR
T1 - Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib combined with trametinib
AU - Long, Georgina V.
AU - Weber, Jeffrey S.
AU - Infante, Jeffrey R.
AU - Kim, Kevin B.
AU - Daud, Adil
AU - Gonzalez, Rene
AU - Sosman, Jeffrey A.
AU - Hamid, Omid
AU - Schuchter, Lynn
AU - Cebon, Jonathan
AU - Kefford, Richard F.
AU - Lawrence, Donald
AU - Kudchadkar, Ragini
AU - Burris, Howard A.
AU - Falchook, Gerald S.
AU - Algazi, Alain
AU - Lewis, Karl
AU - Puzanov, Igor
AU - Ibrahim, Nageatte
AU - Sun, Peng
AU - Cunningham, Elizabeth
AU - Kline, Amy S.
AU - Del Buono, Heather
AU - McDowell, Diane Opatt
AU - Patel, Kiran
AU - Flaherty, Keith T.
PY - 2016/3/10
Y1 - 2016/3/10
N2 - Purpose: To report the overall survival (OS) and clinical characteristics of BRAF inhibitor-naive long-term responders and survivors treated with dabrafenib plus trametinib in a phase I and II study of patients with BRAF V600 mutation-positive metastatic melanoma. Methods: BRAF inhibitor-naive patients treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily (the 150/2 group) from the non-randomly assigned (part B) and randomly assigned (part C) cohorts of the study were analyzed for progression-free and OS separately. Baseline characteristics and factors on treatment were analyzed for associations with durable responses and OS. Results: For BRAF inhibitor-naive patients in the 150/2 groups (n = 78), the progression-free survival at 1, 2, and 3 years was 44%, 22%, and 18%, respectively, for part B (n = 24) and 41%, 25%, and 21%, respectively, for part C (n = 54). Median OS was 27.4 months in part B and 25 months in part C. OS at 1, 2, and 3 years was 72%, 60%, and 47%, respectively, for part B and 80%, 51%, and 38%, respectively, for part C. Prolonged survival was associated with metastases in fewer than three organ sites and lower baseline lactate dehydrogenase. OS at 3 years was 62% in patients with normal baseline lactate dehydrogenase and 63% in patients with a complete response. Conclusion: Dabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma, and approximately 20% were progression free at 3 years. Durable responses occurred in patients with good prognostic features at baseline, which may be predictive.
AB - Purpose: To report the overall survival (OS) and clinical characteristics of BRAF inhibitor-naive long-term responders and survivors treated with dabrafenib plus trametinib in a phase I and II study of patients with BRAF V600 mutation-positive metastatic melanoma. Methods: BRAF inhibitor-naive patients treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily (the 150/2 group) from the non-randomly assigned (part B) and randomly assigned (part C) cohorts of the study were analyzed for progression-free and OS separately. Baseline characteristics and factors on treatment were analyzed for associations with durable responses and OS. Results: For BRAF inhibitor-naive patients in the 150/2 groups (n = 78), the progression-free survival at 1, 2, and 3 years was 44%, 22%, and 18%, respectively, for part B (n = 24) and 41%, 25%, and 21%, respectively, for part C (n = 54). Median OS was 27.4 months in part B and 25 months in part C. OS at 1, 2, and 3 years was 72%, 60%, and 47%, respectively, for part B and 80%, 51%, and 38%, respectively, for part C. Prolonged survival was associated with metastases in fewer than three organ sites and lower baseline lactate dehydrogenase. OS at 3 years was 62% in patients with normal baseline lactate dehydrogenase and 63% in patients with a complete response. Conclusion: Dabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma, and approximately 20% were progression free at 3 years. Durable responses occurred in patients with good prognostic features at baseline, which may be predictive.
UR - http://www.scopus.com/inward/record.url?scp=84962486398&partnerID=8YFLogxK
U2 - 10.1200/JCO.2015.62.9345
DO - 10.1200/JCO.2015.62.9345
M3 - Article
C2 - 26811525
AN - SCOPUS:84962486398
SN - 0732-183X
VL - 34
SP - 871
EP - 878
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -