NSCLC MAGE-A3 immunotherapy development halted

May 4 2016

By Shreeya Nanda

Disease-free survival (DFS) is not prolonged with adjuvant MAGE-A3 immunotherapy in patients with surgically resected non-small-cell lung cancer (NSCLC), according to a placebo-controlled trial.

The MAGE-A3 tumour antigen was targeted via antigen-specific immunotherapy in an earlier phase II trial, with promising results in patients with surgically resected disease, the team explains in The Lancet Oncology.

This phase III trial included 2312 patients with MAGE-A3-positive stage IB, II or IIIA NSCLC who were randomly assigned to either receive up to 13 intramuscular injections of the MAGE-A3 immunotherapeutic, which consists of recombinant MAGE-A3 protein plus the immunostimulant AS15, or placebo over a course of 27 months.

After a median follow-up of 38.1 months in the MAGE-A3 group and 39.5 months in the placebo group, median DFS was comparable in the treatment arms (60.5 and 57.9 months, respectively), as was the median overall survival (OS; not reached in each arm).

When just the subgroup of patients who had not received adjuvant chemotherapy was considered, once again the MAGE-A3 subgroup did not significantly extend DFS or OS relative to placebo.

The incidence of grade 3-5 side effects was identical in the two treatment arms, at 16%, with infections and infestations, vascular disorders and neoplasms the most common high-grade toxicities.

But in the "absence of any treatment effect", the further development of this agent in the NSCLC setting has been stopped, say Johan Vansteenkiste (University Hospital KU Leuven, Belgium) and fellow MAGRIT investigators.

They believe that "[m]ost likely...the limited sample size of the phase 2 randomised trial, in conjunction with possible unnoticed imbalances across groups contributed to the initial positive treatment effect noted."

The study authors add that their findings and those of other phase III vaccination studies raise questions about "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."

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