MAGRIT Trial: recMAGE-A3 + AS15 as Adjuvant Therapy in Resected MAGE-A3–Positive Patients with Lung Cancer
Adjuvant chemotherapy is the standard of care for patients with stage II/IIIA non–small-cell lung cancer (NSCLC), as well as for patients with high-risk stage IB NSCLC; however, this is not applicable to all patients, and the 5-year disease-free survival (DFS) has been suboptimal, underscoring the need for novel therapeutic approaches. The randomized, double-blind, placebo-controlled phase 3 MAGRIT trial evaluated the recMAGE-A3 + AS15 immunotherapy regimen as adjuvant therapy in patients with resected MAGE-A3–positive NSCLC, regardless of previous adjuvant chemotherapy (Vansteenkiste et al. MAGRIT Trial. ESMO 2014: Abstract 1173O). The 3 coprimary end points were DFS in the overall patient population, DFS in the patients with no adjuvant chemotherapy, and DFS in patients with a potentially predictive gene signature.
Of the 13,849 patients screened for the trial, MAGE-A3 was detected in the tumor samples of 4210 patients. Of these, 2272 patients were randomized to receive MAGE-A3 cancer immunotherapy (MAGE-A3 CI) or placebo (13 injections) over a 27-month treatment period. At a median follow-up of 38.8 months, no differences were seen in median DFS between the MAGE-A3 CI and the placebo cohorts (60.5 vs 57.9 months; hazard ratio [HR], 1.024; P = .7379) in the overall population. Similarly, patients who did not receive previous adjuvant chemotherapy did not benefit from the investigational treatment compared with placebo, resulting in a median DFS of 58 months and 56.9 months, respectively (HR, 0.970; P = .7572).
Consistently, no improvement was seen in overall survival between the 2 treatment arms. Subset analysis also did not reveal any survival benefit for any patient subgroups analyzed, including by age, disease stage, histopathology, chemotherapy, tumor region, and MAGE-A3 quantitative expression. The rate of grade 3 or 4 adverse events was similar (16%) between the treatment groups. Common adverse events included pyrexia, injection-site pain, injection-site reaction, fatigue, pain, influenza-like illness, and myalgia, >95% of which were grade 1 or 2 in severity.
These results indicate that immunotherapy with MAGE-A3 in the adjuvant setting did not provide DFS advantage in the overall patient population or in patients who did not receive previous chemotherapy. Vansteenkiste and colleagues concluded that therapeutic vaccination with MAGE-A3 CI represents a promising strategy that was conducted in the appropriate setting, with proper study design and statistical power; however, it is not yet feasible to be used in the setting of NSCLC with the current technology.