| Reference |
Trial |
No. of pts |
Target |
Molecular alteration |
Agent(s) |
Clinical Benefits |
Adverse events |
| Chapman 2011 |
Phase III |
675 |
BRAF |
BRAFV600E mut |
Vemurafenib |
ORR: about 50%; PFS: 5.3 months; OS: 84% at 6 months |
arthralgia, fatigue, cutaneous events, squamous cell carcinoma (SCC), keratoacanthoma (KA), or both |
| Hauschild 2012 |
Phase III |
250 |
BRAF |
BRAFV600 mut |
Dabrafenib |
ORR: about 60%; PFS: 5.1 months; OS: 42% at 5 months |
arthralgia, pyrexia, fatigue, headache, hyperkeratosis, papillomas, palmar-plantar erythrodysesthesia, SCC, KA, basal cell carcinoma, mycosis fungoides |
| Robert 2012 |
Phase III |
322 |
MEK |
BRAFV600 mut |
Trametinib |
ORR: about 22%, PFS: 4.8 months; OS: 81% at 6 months |
rash, diarrhea, nausea, vomiting, fatigue, peripheral edema, alopecia, hypertension, constipation, central serous retinopathy and retinal-vein occlusion |
| Flaherty 2012 |
Phase I/II |
247/162 |
BRAF+ MEK |
BRAFV600E/K mut |
Dabrafenib+ Trametinib |
ORR: about 76%, PFS: 9.4 months; OS: 41% at 12 months |
pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, constipation, and myalgia |
| Ascierto 2013 |
Phase II |
71 |
MEK |
BRAFV600 mut |
MEK162 |
PRR: about 20%, OR+SD: 52% |
rash, diarrhea, acneiform dermatitis, creatine phosphokinase (CK) elevation, fatigue, peripheral edema, central serous retinopathy-like retinal events. |
| NRAS mut |
PRR: about 20%, OR+SD: 63% |
| Catalanotti 2013 |
Phase II |
15 |
MEK |
BRAFV600e/kmut |
Selumetinib |
ORR: about 11%, PFS and OS: data pending |
rash, fatigue, elevated liver function tests, lymphopenia, hypoalbuminemia, dyspnea, cardiac function |
| Carvajal 2013 |
Phase II |
48 |
MEK |
GNAQ mut |
Selumetinib |
ORR: about 15%, PFS and OS: data pending |
CPK elevation, LFT elevation, rash, lymphopenia, edema |
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