Table 2 Clinical trials for genotypes other than BRAF-mutant only

NCT01781572

NRAS

LEE011 MEK162

Cyclin D1/CDK4, cyclin D3/CDK6 MEK

Recruiting

^a

NCT01763164

NRAS

MEK162

MEK

Recruiting

^a

NCT02138292

BRAF WT

Trametinib Digoxin

MEK

cardiac glycoside

Not yet recruiting

^a

NCT01941927

BRAF WT

Trametinib GSK2141795

MEK AKT

Recruiting

^a

NCT00470470

c-KIT

Imatinib

c-KIT

Active

The overall durable response rate was 16% (95% confidence interval (CI), 2–30%), with a median time to progression of 12 weeks (interquartile range (IQR), 6–18 weeks; 95% CI, 11–18 weeks), and a median OS of 46.3 weeks (IQR, 28 weeks-not achieved; 95% CI, 28 weeks-not achieved)

Robert et al (2013)

NCT00631618

c-KIT

Sunitinib

Multiple RTKs

Completed

Of 4 patients with KIT mutations, 1 had a CR for 15 months and 2 had PR (1 and 7 months). 1 of the 6 patients with only KIT amplification or overexpression alone had a PR. In 1 responder with rectal melanoma who later progressed, the recurring tumour had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT

Minor et al (2012)

NCT00591734

Not specified

Everolomus Bevacizumab

mTOR angiogenesis

Completed

12% major response, 58% stable disease, mPFS 4.0 months, OS 8.6 months

Hainsworth et al (2010)

NCT00591734

Not specified

Paclitaxel Carboplatin Everolimus

mTOR

Completed

ORR 17%, PFS 4.04 months, OS 10.12 months

^a

NCT00338130

Not specified

Temozolomide vs Selumetinib

Chemotherapy vs MEK

Active

Selumetinib group: mPFS 78 days, ORR 5.8%

Temozolomide group: mPFS 80 days, ORR 9.4%

Five of the six selumetinib partial responders were BRAF mutated

Kirkwood et al (2012)

NCT00827177

NRAS WT/mutant

Sorafenib Tivantinib

Pan-RAS

c-Met

Completed

CR in 1 pt, PR in 3 pts, and SD in 3 pts. 4 pts had progressive disease and 5 pts were not evaluable. ORR and disease control rate were 25% and 44%, respectively. mPFS was 5.3 mo (95% CI, 1.6–12.9 mo). Among 8 pts with NRAS mutations, mPFS was 9.2 mo (95% CI, 5.3–12.9 mo) and responses were 1 CR, 1 PR and 2 SD

Means-Powell et al (2012)

NCT01363232

BRAF/NRAS

BKM120 MEK162

PI3K

MEK

Active

No results reported

^a

NCT01337765

BRAF/NRAS

BEZ235 MEK162

PI3K

MEK

Active

No results reported

^a

NCT01320085

BRAF/NRAS

MEK162

MEK

Active

No patients had a complete response. Six (20%) of 30 patients with NRAS-mutated melanoma had a partial response (three confirmed) as did 8 (20%) of 41 patients with BRAF-mutated melanoma (two confirmed)

Ascierto et al (2013)

NCT00866177

BRAF/NRAS

Selumetinib

MEK

Completed

Tumour regression was seen in 3/5 patients with BRAF-mutated, low pAKT melanomas; no responses were seen in the high pAKT cohort. The estimated mPFS was 2.2 months in the high pAKT cohort and 7.1 months in the low pAKT cohort

Catalanotti et al (2013)