Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
The Lancet - Early Online Publication, 06/26/2012
Hauschild A et al. – Dabrafenib significantly improved progression-free survival compared with dacarbazine.Methods
- We enrolled patients in this open-label phase 3 trial between Dec 23, 2010, and Sept 1, 2011.
- This report is based on a data cutoff date of Dec 19, 2011.
- Patients aged 18 years or older with previously untreated, stage IV or unresectable stage III BRAFV600E mutation-positive melanoma were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m2 intravenously every 3 weeks).
- Patients were stratified according to American Joint Committee on Cancer stage (unresectable III+IVM1a+IVM1b vs IVM1c).
- The primary endpoint was investigator-assessed progression-free survival and was analysed by intention to treat; safety was assessed per protocol.
- Of the 733 patients screened, 250 were randomly assigned to receive either dabrafenib (187 patients) or dacarbazine (63 patients).
- Median progression-free survival was 5·1 months for dabrafenib and 2·7 months for dacarbazine, with a hazard ratio (HR) of 0·30 (95% CI 0·18—0·51; p<0·0001).
- At data cutoff, 107 (57%) patients in the dabrafenib group and 14 (22%) in the dacarbazine group remained on randomised treatment.
- Treatment-related adverse events (grade 2 or higher) occurred in 100 (53%) of the 187 patients who received dabrafenib and in 26 (44%) of the 59 patients who received dacarbazine.
- The most common adverse events with dabrafenib were skin-related toxic effects, fever, fatigue, arthralgia, and headache.
- The most common adverse events with dacarbazine were nausea, vomiting, neutropenia, fatigue, and asthenia. Grade 3—4 adverse events were uncommon in both groups.