The Pattern of Progression to First-Line Treatment with Dabrafenib and Trametinib in Patients with Unresectable or Metastatic, BRAF-Mutated, Cutaneous Melanoma: Results of the Observational T-WIN Study

SIMPLE SUMMARY: This study collected data from patients with cutaneous melanoma with mutation in the B-RAF gene who were treated with the combination of dabrafenib and trametinib in 34 Italian hospitals in every-day clinical practice. The aim was to understand how these drugs modify the progression pattern of the tumor in a heterogeneous population of patients who had either a limited (104 patients) or a bulky disease (97 patients). The results showed that fewer patients had lesions at the skin and more patients had lesions in other sites rather than the skin and lymph nodes when the disease progressed compared to baseline, and the proportion of patients with at least three involved organs at the progression increased in both cohorts. The survival and the time without progression were similar to previously published data and no new adverse reactions were reported. Therefore, dabrafenib and trametinib demonstrated to be effective and safe in heterogenous patients. ABSTRACT: In patients with B-RAF-mutated cutaneous melanoma, targeted therapies are the treatment of choice to achieve a rapid response. In this multicentric, prospective, observational study, patients with B-RAF-mutated cutaneous melanoma who were treated with dabrafenib and trametinib were categorized in two cohorts (cohort A: limited disease (n = 104) and cohort B: bulky disease (n = 97)) according to lactate dehydrogenase levels. The primary endpoint was the progression pattern; the secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety data. From baseline to time of progression, there was a progression from nodal to other sites of disease in cohort A and from skin and nodal to other sites in cohort B. In both the cohorts, the number of involved organs and metastases at each location decreased. The median OS was 32.4 months (95% CI: 20.1 months (not estimable)) for cohort A, and 10.5 months (95% CI: 8.3–14.4 months) for cohort B; median PFS was 12.4 months (95% CI: 10.9–17.0 months) for cohort A, and 8.1 months (95% CI: 6.3–9.4 months) for cohort B. No new safety signals were reported. This study describes the patterns of first-line treatment progression with dabrafenib and trametinib in Italian clinical practice. The effectiveness and safety data were consistent with previous trials and extended to a real-world heterogeneous population.