Dreno B, et al. - Researchers assessed the efficacy of the MAGE-A3 immunotherapeutic as adjuvant therapy for patients with stage IIIB or IIIC melanoma. They found that in an adjuvant setting, an antigen-specific immunotherapeutic alone was not efficacious. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped.

Methods

• Researchers performed a phase 3, double-blind, randomized, placebo-controlled trial (DERMA) in 31 countries and 263 centers, and included patients aged 18 years or older and having histologically proven, completely resected, stage IIIB or IIIC, MAGE-A3-positive cutaneous melanoma with macroscopic lymph node involvement and an Eastern Cooperative Oncology Group performance score of 0 or 1.
• Patients (2:1) were assigned to receive up to 13 intramuscular injections of recombinant MAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic; 300 μg MAGE-A3 antigen plus 420 μg CpG 7909 reconstituted in AS01B to a total volume of 0·5 mL), or placebo, over 27-months: five doses at 3-weekly intervals, followed by eight doses at 12-weekly intervals.
• Disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive) previously identified and validated here via an adaptive signature design were included as co-primary outcomes.
• Final analyses were carried out involving all patients who had received at least one dose of study treatment; analyses for efficacy were in the as-randomized population and for safety were in the as-treated population.

Results

• Data showed a total of 3,914 patients were screened, 1,391 randomly assigned, and 1,345 started treatment (n=895 for MAGE-A3 and n=450 for placebo) between December 1, 2008, and September 19, 2011.
• The median follow-up of 28.0 months [IQR 23.3–35.5] in the MAGE-A3 group and 28.1 months [23.7–36.9] in the placebo group was reported at the final analysis (data cutoff May 23, 2013).
• In the MAGE-A3 group and in the placebo group (hazard ratio [HR] 1.01, 0.88–1.17, p=0.86), the observed median disease-free survival was 11.0 months (95% CI 10.0–11.9) and 11.2 months (8.6–14.1), respectively.
• In the GS-positive population, the MAGE-A3 group had median disease-free survival of 9.9 months (95% CI 5.7–17.6) and placebo group had median disease-free survival of 11.6 months (5.6–22.3) (HR 1.11, 0.83–1.49, p=0.48).
• A total of 126 (14%) of 894 patients in the MAGE-A3 group and 56 (12%) of 450 patients in the placebo group experienced adverse events of grade 3 or worse within the first 31 days of treatment; during this period, treatment-related adverse events of grade 3 or worse were experienced by 36 (4%) patients given MAGE-A3 vs six (1%) patients given placebo, and 14% of patients in both groups reported at least one serious adverse event (129 patients given MAGE-A3 and 64 patients given placebo).
• Neoplasms (33 [4%] patients in the MAGE-A3 group vs 17 [4%] patients in the placebo group), general disorders and administration site conditions (25 [3%] for MAGE-A3 vs four [< 1%] for placebo) and infections and infestations (17 [2%] for MAGE-A3 vs seven [2%] for placebo) constituted the most common adverse events of grade 3 or worse.
• No deaths related to treatment were reported.