Research in context
Evidence before this study
We searched PubMed on Dec 1, 2015, using the following terms: “NSCLC AND (vaccine OR immunotherapeutic) AND clinical trials, phase III” without date or language limitations. We identified two studies, one with a whole tumour cell vaccine (belagenpumatucel-L) in advanced non-small-cell lung cancer (NSCLC), and one with a MUC-1 mucoprotein directed liposomal vaccine (L-BLP25, tecemotide) in locally advanced NSCLC in disease control after chemoradiotherapy. Both studies were negative for their primary endpoint.
Added value of this study
Fewer than half of the patients with completely resected NSCLC are cured, the others experience cancer relapse that is often fatal. During the past decades, several adjuvant treatments to improve prognosis of these patients have been studied. Adjuvant radiotherapy was not beneficial. The improvement of outcome by postoperative cisplatin-based chemotherapy was clearly established in meta-analyses of chemotherapy adjuvant trials. Efforts to improve the efficacy ratio of treatment based on biomarkers have failed up to now. By contrast with the major progress brought by molecularly targeted agents for patients with advanced NSCLC over the last years, no further progress in adjuvant chemotherapy for patients with resected NSCLC has been made.
Therapeutic cancer vaccination has the potential to eliminate remaining cancer cells after complete resection, thereby decreasing relapse rates and improving survival. Early signs with the MAGE-A3 immunotherapeutic in a randomised placebo-controlled phase 2 study suggested clinical activity in resected NSCLC. No other clinical studies of adjuvant immunotherapy were available at the time of the design of MAGRIT.
With almost 14 000 surgical patients screened, MAGRIT is the largest therapeutic trial ever done in the adjuvant setting of NSCLC. Unfortunately, the MAGE-A3 immunotherapeutic did not increase survival in patients with resected NSCLC. The study provides important insights into the clinical characteristics, cancer recurrence, and survival in patients with contemporary thoracic surgery and chemotherapy.
Implications of all the available evidence
Up to now, except for adjuvant cisplatin-based chemotherapy, no other strategy could improve the outcome of patients with resected NSCLC. Phase 3 studies done in patients with NSCLC, including MAGRIT, confirm the acceptable clinical safety profile of cancer immunotherapeutics, but did not improve overall survival. These results question whether therapeutic cancer vaccination with the current technology is able to surmount the immunosuppressive environment of lung cancer and have implications for the conduct of future studies assessing cancer immunotherapies in NSCLC. At present, only TG4010, an attenuated vaccinia Ankara virus expressing MUC-1 and interleukin 2, remains in clinical development (NCT01383148).