Phase II, Open-Label, Randomized Trial of the MEK 1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma
Mené sur 200 patients atteints d'un mélanome non résécable de stade III/IV, cet essai de phase II compare l'efficacité et la toxicité du selumetinib et du temozolomide
Purpose: To compare the efficacy and tolerability of the MEK 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naïve patients with unresectable stage III/IV melanoma. Methods: This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m2/day for 5 days, then 23 days off treatment). The primary endpoint was progression-free survival. Results: Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86-1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (9.4%) patients in the temozolomide group. Among patients with BRAF mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). However, five of the six selumetinib partial responders were BRAF mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%) and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%) and vomiting (44.2%) were reported with temozolomide. Conclusions: No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for BRAF/NRAS mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had BRAF mutant tumors.