Table 1.
Comparison of clinical trials studying BRAF/MEK inhibitors
| Trial | Drug | Median PFS (months) | Median OS (months) | Adverse effects |
|---|---|---|---|---|
| BRIM310 | Vemurafenib | 5.3 | 13.6 | Most common: cutaneous events (photosensitivity, blistering), arthralgia, and fatigue Major: arthralgia, rash, fatigue, cutaneous squamous-cell carcinoma, keratoacanthoma, nausea, pruritis, hyperkeratosis, diarrhea, headache, vomiting, and neutropenia |
| BREAK-312 | Dabrafenib | 5.1 | 20 | Most common: cutaneous events (hyperkeratosis, papillomas, PPED), pyrexia, fatigue, headache, and arthralgia Major: hyperkeratosis, PPED, cSCC, keratoacanthoma, nausea, vomiting, neutropenia, and thrombocytopenia |
| METRIC44 | Trametinib | 4.8 | N/A | Most common: rash (papulopustular), diarrhea, peripheral edema, fatigue, and dermatitis acneiform Major: rash, fatigue, peripheral edema, acneiform dermatitis, nausea, alopecia, hypertension, constipation, central serous retinopathy, and retinal vein occlusion |
| COMBI-d35 | Dabrafenib | 8.8 | 18.7 | Most common: hyperkeratosis, fatigue, PPED, alopecia, pyrexia, arthralgia Major: pyrexia, chills, fatigue, rash, nausea, diarrhea, vomiting, hyperkeratosis, and PPED |
| Dabrafenib + trametinib | 11 | 25.1 | Most common: pyrexia, chills, fatigue, rash, and nausea Fewer cSCC, hyperkeratosis, skin papillomas, alopecia, and PPED Pyrexia more common Major: pyrexia, fatigue, diarrhea, arthralgia, vomiting, peripheral edema, and PPED | |
| COMBI-v24 | Vemurafenib | 7.3 | 18 | Most common: arthralgia, rash, alopecia, diarrhea, nausea, and fatigue Major: pyrexia, nausea, diarrhea, vomiting, arthralgia, rash, alopecia, PPED, hyperkeratosis, skin papilloma, and photosensitivity |
| Dabrafenib + trametinib | 11.4 | 25.6 | Most common: pyrexia, nausea, diarrhea, chills, fatigue, headache, and vomiting Pyrexia more common Fewer rash, photosensitivity, PPED, skin papillomas, cSCC, keratoacanthoma, and hyperkeratosis Major: pyrexia, nausea, diarrhea, chills, vomiting, arthralgia, and rash | |
| coBRIM31 | Vemurafenib | 7.2 | 17.4 | Most common: rash, arthralgia, diarrhea, fatigue, alopecia, hyperkeratosis, nausea, pyrexia, decreased appetite, photosensitivity, and serous retinopathy Major: rash, arthralgia, diarrhea, fatigue, alopecia, hyperkeratosis, nausea, decreased appetite, and vomiting |
| Vemurafenib + cobimetinib | 12.3 | 22.3 | Most common: rash, diarrhea, nausea, arthralgia, fatigue, photosensitivity, pyrexia, vomiting, serous retinopathy, alopecia, and hyperkeratosis Fewer cSCC, keratoacanthoma, and Bowen’s disease Photosensitivity more common Serous retinopathy, decreased LVEF, and increased CPK level | |
| COLUMBUS part 134,36,37 | Vemurafenib | 7.3 | 16.9 | Major: arthralgia |
| Encorafenib | 9.6 | N/A | Major: PPED, myalgia, arthralgia, vomiting, nausea | |
| Encorafenib + binimetinib | 14.9 | 33.6 | More common: GI (diarrhea, constipation, vomiting, abdominal pain), asymptomatic CPK increase, and blurred vision Less common: skin toxicity (pruritis, hyperkeratosis, rash, keratosis pilaris, palmoplantar keratoderma, PPED, dry skin, skin papilloma, maculopapular rash, and sunburn), alopecia, photosensitivity, arthralgia, myalgia, extremity pain, decreased appetite, musculoskeletal pain, and decreased weight Major: elevated GGT, elevated CPK, HTN, and pyrexia | |
| COLUMBUS part 238 | Encorafenib (Encorafenib part 1+2) | 7.4 9.2 | N/A | |
| Encorafenib + binimetinib | 12.9 | N/A |
Abbreviations: cSCC, cutaneous squamous cell carcinoma; GI, gastrointestinal; OS, overall survival; PPED, palmar-plantar erythrodysesthesia; LVEF, left ventricular ejection fraction; CPK, creatine phosphokinase; N/A, not applicable.