A Retrospective Analysis of Dabrafenib and/or Dabrafenib Plus Trametinib Combination in Patients with Metastatic Melanoma to Characterize Patients with Long-Term Benefit in the Individual Patient Program (DESCRIBE III)

Abstract

Simple Summary Compassionate-use programs provide an opportunity to retrospectively evaluate the treatment patterns and clinical outcomes in a real-world setting to validate the results derived from controlled randomized clinical trials. The COMBI-d and COMBI-v studies established the superior efficacy of dabrafenib + trametinib (dab + tram) versus BRAF inhibitor monotherapy in patients with BRAF V600–mutant metastatic melanoma. In light of their five-year results demonstrating long-term benefit with first-line dab + tram, it is important to get a real-world perspective of the long-term treatment duration for dab + tram. DESCRIBE III was designed to retrospectively evaluate the impact of patient characteristics on the long-term outcomes of dab + tram in a real-world setting based on the duration of clinical benefit. Consistent with the findings from the pooled analysis of COMBI-d and COMBI-v, lower LDH level and <3 metastatic sites at baseline were associated with a longer duration of treatment benefit in a real-world setting. Abstract The dabrafenib plus trametinib (dab + tram) combination has demonstrated durable long-term efficacy in patients with BRAF V600–mutant metastatic melanoma. However, real-world data characterizing patients with long-term benefit are limited. DESCRIBE III was a global, observational, retrospective, chart review study in patients with unresectable or metastatic melanoma treated with dab monotherapy and/or dab + tram combination therapy as part of the Named Patient Program or Individual Patient Program. Overall, 509 patients were enrolled. Patients were categorized into three groups based on their observed treatment duration: long-term (on therapy ≥12 months), intermediate (on therapy ≥6 months and <12 months), and short-term (on therapy <6 months) duration of benefit. More patients in the short-term duration of benefit group had baseline characteristics associated with poor prognosis compared with the other two groups. Median lactate dehydrogenase (LDH) levels (368 U/L) at baseline were also higher in the short-term duration of benefit group. No new safety signals were identified. DESCRIBE III identified baseline characteristics associated with long-term benefit of dab + tram. Lower LDH level and <3 metastatic sites at baseline were associated with a longer duration of benefit, confirming that the findings from COMBI-d and COMBI-v are relevant to patients treated in a real-world setting.