- Results from a multicenter, open-label, randomized controlled phase 2 trial suggest that adding trametinib to paclitaxel chemotherapy is associated with improved PFS and objective response rate (ORR), but not OS, in patients with advanced, BRAF-wild-type melanoma.
Why this matters
- Evidence that adding the kinase inhibitor trametinib may improve paclitaxel chemotherapy in patients who do not benefit from BRAF inhibitor therapy.
- Trametinib/paclitaxel was associated with longer PFS (time ratio [TR], 1.47; P=.04) and ORR (OR, 4.7; P=.01) compared with paclitaxel alone.
- Trametinib/paclitaxel was not associated with OS (TR, 0.71; P=.18).
- Pazopanib (Votrient)/paclitaxel was not associated with PFS (TR, 1.36; P=.14), ORR (OR, 1.82; P=.34), or OS (TR, 0.87; P=.34) compared with paclitaxel alone.
- Grade 3+ adverse events were experienced by 24% of patients in the paclitaxel-alone group, 75% of patients in the trametinib/paclitaxel group, and 78% of patients in the pazopanib/paclitaxel group.
- 111 patients with advanced, BRAF-wild-type melanoma were randomly assigned 1:1:1 to paclitaxel alone (n=38), paclitaxel and trametinib (n=36), or paclitaxel and pazopanib (n=37) and analyzed for efficacy and safety.
- Funding: GlaxoSmithKline/Novartis; UK National Cancer Research Network.
- Open-label study.
- No placebo control.