Dabrafenib plus trametinib

A multinational double-blind trial (COMBI-AD [NCT01682083]) included patients with stage IIIA, IIIB, or IIIC melanoma with BRAF V600E or V600K pathogenic variants who underwent completion lymphadenectomy. Patients were randomly assigned (1:1) to receive either dabrafenib plus trametinib or two matched placebo tablets.[26] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. Patients with resection occurring more than 12 weeks before random assignment and an ECOG PS score higher than 1 were excluded. Dabrafenib was given at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy) for 12 months in the absence of disease recurrence, unacceptable toxic effects, or death. A total of 870 patients were randomly assigned (438 patients to combination therapy and 432 patients to placebo). Baseline characteristics were balanced in the two treatment groups. Most patients (91%) had BRAF V600E pathogenic variants compared with 9% who had BRAF V600K variants. Most patients (92%) had an ECOG PS of 0.

A multinational double-blind trial (COMBI-AD [NCT01682083]) included patients with stage IIIA, IIIB, or IIIC melanoma with BRAF V600E or V600K pathogenic variants who underwent completion lymphadenectomy. Patients were randomly assigned (1:1) to receive either dabrafenib plus trametinib or two matched placebo tablets.[26] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. Patients with resection occurring more than 12 weeks before random assignment and an ECOG PS score higher than 1 were excluded. Dabrafenib was given at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy) for 12 months in the absence of disease recurrence, unacceptable toxic effects, or death. A total of 870 patients were randomly assigned (438 patients to combination therapy and 432 patients to placebo). Baseline characteristics were balanced in the two treatment groups. Most patients (91%) had BRAF V600E pathogenic variants compared with 9% who had BRAF V600K variants. Most patients (92%) had an ECOG PS of 0.

At the data cutoff date for the primary analysis, the minimum follow-up was 2.5 years (median, 2.8 years), and all patients had completed trial treatment. Disease recurrence occurred in 163 of 438 patients (37%) who received combination therapy and in 247 of 432 patients (57%) who received placebo (HRrelapse or death, 0.47; 95% CI, 0.39–0.58; P < .001). Median RFS had not been reached in the combination arm (95% CI, 44.5–not reached) and was 16.6 months (95% CI, 12.7–22.1) in the placebo group.[26][Level of evidence B1]

A multinational double-blind trial (COMBI-AD [NCT01682083]) included patients with stage IIIA, IIIB, or IIIC melanoma with BRAF V600E or V600K pathogenic variants who underwent completion lymphadenectomy. Patients were randomly assigned (1:1) to receive either dabrafenib plus trametinib or two matched placebo tablets.[26] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. Patients with resection occurring more than 12 weeks before random assignment and an ECOG PS score higher than 1 were excluded. Dabrafenib was given at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy) for 12 months in the absence of disease recurrence, unacceptable toxic effects, or death. A total of 870 patients were randomly assigned (438 patients to combination therapy and 432 patients to placebo). Baseline characteristics were balanced in the two treatment groups. Most patients (91%) had BRAF V600E pathogenic variants compared with 9% who had BRAF V600K variants. Most patients (92%) had an ECOG PS of 0.

In the combination therapy arm, 26% of the patients had an adverse event leading to the discontinuation of therapy, 38% required dose reduction, and 66% required dose interruption. In the placebo arm, 3% of the patients had an adverse event leading to discontinuation of therapy, 3% required dose reduction, and 15% required dose interruption. Serious adverse events occurred in 36% of the patients who received the combination therapy and 10% of the patients in the placebo group. One death, which resulted from pneumonia, was reported in the combination therapy arm.

A multinational double-blind trial (COMBI-AD [NCT01682083]) included patients with stage IIIA, IIIB, or IIIC melanoma with BRAF V600E or V600K pathogenic variants who underwent completion lymphadenectomy. Patients were randomly assigned (1:1) to receive either dabrafenib plus trametinib or two matched placebo tablets.[26] The primary end point was RFS, defined as time from randomization until the date of first recurrence or death from any cause. Patients with resection occurring more than 12 weeks before random assignment and an ECOG PS score higher than 1 were excluded. Dabrafenib was given at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy) for 12 months in the absence of disease recurrence, unacceptable toxic effects, or death. A total of 870 patients were randomly assigned (438 patients to combination therapy and 432 patients to placebo). Baseline characteristics were balanced in the two treatment groups. Most patients (91%) had BRAF V600E pathogenic variants compared with 9% who had BRAF V600K variants. Most patients (92%) had an ECOG PS of 0.

A final analysis performed after a minimum of 8.33 years of follow-up showed superior RFS for patients who received the dabrafenib plus trametinib combination compared with patients who received placebo. Of patients who received the combination, 52% (95% CI, 47.4%–56.3%) were alive without relapse compared with 36% (95% CI, 30.9%–40.2%) of patients who received the placebo (HR, 0.52; 95% CI, 0.43–0.63). DMFS was also improved in patients who received the combination (60% vs. 46%; HR, 0.56; 95% CI, 0.44–0.71). An OS analysis showed improvement that was not statistically significant (HR, 0.80; 95% CI, 0.62–1.01).[31,32]