Efficacy
COMBI-d
At data cut-off, 3-year PFS was significantly longer in the combination dabrafenib-trametinib versus dabrafenib-placebo arm (22% vs 12%; HR 0.71, 95% CI, 0.57 to 0.88).r
3-year OS analysis showed the combination arm achieved benefit compared to the dabrafenib arm 44% vs 32% respectively (HR 0.75, 95% CI, 058 to 0.96). 25 (12%) patients on the dabrafenib monotherapy arm crossed over to dabrafenib-trametinib and 6 (24%) had progressed on monotherapy before crossover. All crossover patients remained on dabrafenib-trametinib at data cut-off, and survival outcomes continued to be followed up under the monotherapy arm.r
Post-progression systemic therapy was greater in the dabrafenib monotherapy arm than with dabrafenib-trametinib (62% vs 48%). In both the dabrafenib-trametinib and monotherapy groups, immunotherapy was the most common subsequent anticancer therapy (56% vs 56%), ipilimumab being the most common immunotherapy (41% vs 50%) with fewer anti-PD-1 treatments with nivolumab (7% vs 5%) and pembrolizumab (13% vs 11%).r
Progression free survivalr
aIncludes 25 patients who crossed over from monotherapy to the combination.
bOf D+T patients who were progression free at 3 years, 28 (90%) remained on D+T.
© Annals of Oncology 2017
Overall survivalr
aIncludes 25 patients who crossed over from monotherapy to the combination.
bOf D+T patients who were progression free at 3 years, 28 (90%) remained on D+T.
© Annals of Oncology 2017
Pooled analysis of COMBI-d and COMBI-v
In the pooled analysis of patients randomised to dabrafenib-trametinib, at a median follow up of 22 months, the median PFS was 11.1 months (95% CI, 9.5-12.8). The PFS rates were 21% (95% CI, 17-24) at 4 years, and 19% (95% CI, 15-22) at 5 years. Patients with a normal baseline lactate dehydrogenase (LDH) had a greater 5-year PFS rate of 25% (95% CI, 20-30), compared to 8% (95% CI, 4-13) in patients with an elevated baseline LDH.r
Progression free survivalr
© N Engl J Med 2019
Across the trials, median OS was 25.9 months (95% CI, 22.6-31.5) in patients treated with dabrafenib-trametinib. The OS rates were 37% (95% CI, 33-42) at 4 years, and 34% (95% CI, 30-38) at 5 years. The 5-year OS was 43% in patients with a normal baseline LDH (95% CI, 38-49) compared with 16% in those with elevated LDH (95% CI, 11-22). Patients with normal LDH and fewer than three organ sites of metastasis had an estimated 5-year OS of 55% (95% CI, 48-61). Factors associated with OS by multivariate analysis were consistent with those associated with PFS.r
Overall survivalr
© N Engl J Med 2019
Objective response to treatment with combination therapy was seen in 68% (n = 383) of patients, with complete response in 19% (n = 109). The 5-year OS was 71% (95% CI, 62-79) in patients with a complete response, 32% (95% CI, 26-37) in those with a partial response and 16% (95% CI, 10-24) in those with stable disease.r