CHICAGO -- An investigational immunotherapy that targets an antigen produced by non-small-cell lung cancer (NSCLC) tended to reduce the risk of recurrence by 27% when used as adjuvant therapy with surgery.
CHICAGO, June 6 -- An investigational immunotherapy that targets an antigen produced by non-small-cell lung cancer (NSCLC) tended to reduce the risk of recurrence by 27% when used as adjuvant therapy with surgery.
Results of the multicenter, proof-of-principle trial with the fusion protein-derived agent MAGE-A3 have set the stage for a global phase III trial that will involve more than 2,000 patients, said Johan Vansteenkiste, M.D., of the University of Leuven in Belgium.
"This immunotherapy works somewhat like a vaccine," Dr. Vanasteenkiste told attendees at the American Society of Clinical Oncology meeting here. "The target is tumor specific, so there are no adverse reactions in the rest of the body. The agent is very well tolerated."
Acknowledging that theirs was only a phase II trial and that the data did not reach statistical significance, Dr. Vanasteenkiste said it still signaled a benefit. "The signal we have is that this immunotherapeutic agent reduces the risk of relapse," he said, "and improves survival to the same degree as adjuvant chemotherapy."
The trial involved 182 patients with stage IB/II NSCLC. All of the patients had tumors that expressed MAGE-A3, an antigen produced by 35% to 50% of early NSCLC. Following curative resection, patients were randomized in a 2:1 ratio to MAGE-A3 or placebo.
The patients were followed for as long as 5 years, and the primary endpoint was disease-free survival. In developing the study protocol, investigators assumed a 40% recurrence rate at 30 months with placebo and a 10% absolute decrease (25% relative decrease) in the risk of recurrence with MAGE-A3.
The 122 patients randomized to active therapy began treatment with an induction phase of 300 mg MAGE-A3 IM every 3 weeks for five cycles followed by maintenance therapy consisting of the same dose administered every 3 months for eight cycles. Placebo patients followed the same treatment schedule.
At a median follow-up of 28 months, the MAGE-A3 group had a recurrence rate of 30.6% versus 43.3% for the placebo group, which translated into a 27% reduction in the hazard ratio but was not statistically significant (p=0.093).
Mortality was 21.3% with MAGE-A3 and 31.6% with surgery alone (p=0.088). The duration of the disease-free interval also favored MAGE-A3 but did not reach statistical significance (HR 0.73, p=0.107).
Dr. Vansteenkiste said MAGE-A3 was well tolerated and most adverse events were grade 1-2. The most common adverse events were injection-site reactions, fever, fatigue, and muscle pain.
Grade 3-4 events occurred in fewer than 10% of MAGE-A3 treatment cycles, and only three events were potentially related to the immunotherapeutic agent. One patient in the MAGE-A3 group withdrew because of worsening COPD.
Putting the results into perspective, Dr. Vansteenkiste noted that platinum-based chemotherapy is the generally accepted adjuvant systemic therapy for NSCLC and results in about a 16% improvement in disease-free survival. However, only about half of patients complete four courses of cisplatin-based chemotherapy.
"Most patients with early-stage non-small-cell lung cancer have surgery, but only about half of them are cured, so we could do better," said Dr. Vansteenkiste. "We tried adjuvant radiation therapy, and that didn't work. Then we tried adjuvant chemotherapy, and it took us 10 years to find out that it works-but with a lot of toxicity. As compared to chemotherapy, this immunotherapeutic agent is very well tolerated."
Enrollment in the global phase III trial of adjuvant MAGE-A3 in NSCLC will begin this month, according to a statement from manufacturer GlaxoSmithKline. The placebo-controlled trial has an enrollment target of 2,270 patients, and the primary endpoint is disease-free survival.