MAGE-A3 Immunotherapeutic as Adjuvant Therapy for MAGE-A3–Positive Stage III Melanoma
In the phase III DERMA trial reported in The Lancet Oncology, Dreno et al found that an adjuvant MAGE-A3 immunotherapeutic provided no benefit vs placebo in patients with resected MAGE-A3–positive stage IIIB or IIIC melanoma. Development of the agent for use in melanoma has been stopped.
The MAGE-A3 cancer-testis tumor antigen is expressed in the majority of melanomas. The MAGE-A3 immunotherapeutic consists of a recombinant MAGE-A3 protein given with the immunostimulant AS15 and was designed to enhance humoral and cell-mediated immune responses against MAGE-A3–expressing cells.
Study Details
In the double-blind trial, 1,391 patients with stage IIIB or IIIC disease from 263 sites in 31 countries were randomized 2:1 between December 2008 and September 2011 to receive MAGE-A3 immunotherapeutic (n = 921) or placebo (n = 470). Patients in the MAGE-A3 group received up to 13 intramuscular injections over a 27-month period, consisting of 5 doses at 3-week intervals followed by 8 doses at 12-week intervals.
The co-primary outcomes were disease-free survival in the overall population and in patients with a potentially predictive gene signature (GS-positive).
At final analysis, median follow-up was 28 months. Median disease-free survival was 11.0 months in the MAGE-A3 group vs 11.2 months in the placebo group (hazard ratio [HR] = 1.01, P = .86). In the GS-positive population (316 MAGE-A3 patients, 116 placebo patients), median disease-free survival was 9.9 months vs 11.6 months (HR = 1.11, P = .48).
Adverse Events
Within the first 31 days of treatment, grade ≥ 3 adverse events occurred in 14% of the MAGE-A3 group and 12% of the placebo group (considered treatment-related in 4% vs 1%), with the most common being neoplasms (4% vs 4%); general disorders and administration site conditions (3% vs < 1%); and infections and infestations (2% vs 2%). Serious adverse events were reported in 14% of both groups. No treatment-related deaths were reported.
The investigators concluded, “An antigen-specific immunotherapeutic alone was not efficacious in this clinical setting. Based on these findings, development of the MAGE-A3 immunotherapeutic for use in melanoma has been stopped.”
The study was funded by GlaxoSmithKline Biologicals SA.
Fernando Ulloa-Montoya, PhD, of GlaxoSmithKline, Rixensart, Belgium, is the corresponding author for The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
