Trametinib

A total of 1,022 patients were screened for BRAF pathogenic variants, resulting in 322 eligible patients (281 with BRAF V600E, 40 with BRAF V600K, and one with both variants).[24] One previous treatment (biological or chemotherapy) was allowed; however, no previous treatment with a BRAF or MEK inhibitor was permitted. Patients were randomly assigned in a 2:1 ratio to receive either trametinib (2 mg every day) or IV chemotherapy (either dacarbazine 1,000 mg/m2 every 3 weeks or paclitaxel 175 mg/m2 every 3 weeks). Crossover for patients randomly assigned to chemotherapy was allowed. The primary end point was PFS.

A total of 1,022 patients were screened for BRAF pathogenic variants, resulting in 322 eligible patients (281 with BRAF V600E, 40 with BRAF V600K, and one with both variants).[24] One previous treatment (biological or chemotherapy) was allowed; however, no previous treatment with a BRAF or MEK inhibitor was permitted. Patients were randomly assigned in a 2:1 ratio to receive either trametinib (2 mg every day) or IV chemotherapy (either dacarbazine 1,000 mg/m2 every 3 weeks or paclitaxel 175 mg/m2 every 3 weeks). Crossover for patients randomly assigned to chemotherapy was allowed. The primary end point was PFS.

The investigator-assessed PFS was 4.8 months in patients who received trametinib and 1.5 months in patients who received chemotherapy (HR for PFS or death, 0.45; 95% CI, 0.33–0.63; P < .001). A radiology review blinded-to-treatment arm resulted in similar outcomes. Median OS has not been reached.

A total of 1,022 patients were screened for BRAF pathogenic variants, resulting in 322 eligible patients (281 with BRAF V600E, 40 with BRAF V600K, and one with both variants).[24] One previous treatment (biological or chemotherapy) was allowed; however, no previous treatment with a BRAF or MEK inhibitor was permitted. Patients were randomly assigned in a 2:1 ratio to receive either trametinib (2 mg every day) or IV chemotherapy (either dacarbazine 1,000 mg/m2 every 3 weeks or paclitaxel 175 mg/m2 every 3 weeks). Crossover for patients randomly assigned to chemotherapy was allowed. The primary end point was PFS.

Adverse events leading to dose interruptions occurred in 35% of patients in the trametinib group and 22% of those in the chemotherapy group. Adverse events leading to dose reductions occurred in 27% of patients who received trametinib and in 10% of those who received chemotherapy.

A total of 1,022 patients were screened for BRAF pathogenic variants, resulting in 322 eligible patients (281 with BRAF V600E, 40 with BRAF V600K, and one with both variants).[24] One previous treatment (biological or chemotherapy) was allowed; however, no previous treatment with a BRAF or MEK inhibitor was permitted. Patients were randomly assigned in a 2:1 ratio to receive either trametinib (2 mg every day) or IV chemotherapy (either dacarbazine 1,000 mg/m2 every 3 weeks or paclitaxel 175 mg/m2 every 3 weeks). Crossover for patients randomly assigned to chemotherapy was allowed. The primary end point was PFS.

The most common adverse events included rash, diarrhea, nausea, vomiting, fatigue, peripheral edema, alopecia, hypertension, and constipation. Cardiomyopathy (7%), interstitial lung disease (2.4%), central serous retinopathy (<1%), and retinal-vein occlusion (<1%) are uncommon but serious adverse events associated with trametinib. On-study cutaneous SCCs were not observed. For more information, visit Fatigue and Nausea and Vomiting Related to Cancer Treatment.