Skip to main content

Table 1 Systemic melanoma therapies: Phase III clinical trial outcomes

From: Liquid biomarkers in melanoma: detection and discovery

Therapy ORR Median PFS (months); % survival (year) Median OS (months); % survival (year) Grade 3/4 toxicity Biomarkers examined Reference
Molecular therapies
Vemurafenib1 (n = 337) 48% 6.9; 14% (1.5 years) 13.6; 39% (1.5 years) 73% BRAF V600 mutation and LDH [131] [132, 133]
Dabrafenib1 (n = 187) 50% 5.1; 12% (3 years) 20; 45% (2 years) 53%¥ BRAF V600 mutation and LDH [134] [135, 136]
Trametinib2 (n = 214) 22% 4.8; NR NR; 81% (6 months) NR BRAF V600 mutation and LDH [137] [138]
Dabrafenib + trametinib (n = 352) 64% 12.1; 30% (2 years), 24% (3 years) 25.6; 73% (1 year), 52% (2 years), 44% (3 years) 52% BRAF V600 mutation and LDH [139] [139, 140]
Vemurafenib + cobimetinib2(n = 247) 70% 12.3; NR 22.3; 75% (1 year), 48% (2 years) 60% Ki67, p56, MAPK, PI3K pathways, cell proliferation, CD8 T cells [141] [141]
Immunotherapies
gp1003 (n = 136)* 1.5% 2.8; 48.5% (12 weeks) 6.4; 25.3% (1 year), 13.7% (2 years) 11.4% LDH [3] [3]
Ipilimumab4 (n = 278) 13% 2.8; 14% (2 years) 16.0; 43% (2 years) 20% LDH, peripheral blood absolute lymphocyte count [142] [6, 143]
gp100 + ipilimumab (n = 403)* 5.7% 2.8; 49.1% (12 weeks) 10; 44% (1 year), 21.6% (2 years) 17.4% LDH [3] [3]
Nivolumab5 (n = 210) 40% 5.1; 44% (1 year) Not reached; 73% (1 year) 11.7% Tumor cell PD-L1 expression, peripheral blood absolute lymphocyte count [142] [144]
Pembrolizumab5 (n = 277) 36% 4.1; 28% (2 years) Not reached; 55% (2 years) 17% LDH, blood count parameters [129] [6, 143]
Ipilimumab + nivolumab (n = 314) 57.6% 11.5; 49% (1 year), 39% (3 years) Not reached; 64% (2 years), 58% (3 years) 55% Tumor cell PD-L1 expression, peripheral blood absolute lymphocyte count [142] [7, 145]
T-VEC6 (n = 295) 26.4%** NR 23.3; 50% (2 years) 36% None [146]
  1. ORR, objective response rate; NR, Not reported; PFS, progression free survival; OS, overall survival. Grade 3/4 toxicity as defined by the American National Institute of Health and National Cancer Institute’s Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). *PFS only available at 12 weeks; ** Durable response rate was used and not standard RECIST criteria; ¥Grade ≥ 2 only, as grade 3/4 not reported
  2. 1Dabrafenib and vemurafenib are selective BRAFV600 inhibitors. 2Trametinib and cobimetinib are inhibitors of MEK1/2. 3gp100 is a human melanoma peptide vaccine. 4Ipilimumab is an antibody targeting the CTLA-4 receptor. 5Nivolumab and pembrolizumab are antibodies targeting the PD-1 receptor. 6T–VEC (talimogene laherparepvec) is a genetically engineered oncolytic virus. LDH denotes lactate dehydrogenase