ELCC: Immunotherapy for NSCLC Well-Tolerated

By Michael Smith
GENEVA, 26 april 2008-- An immune-boosting treatment for non-small-cell lung cancer patients with completely resected stage IB or II disease is safe and well tolerated, researchers said here. The 44-week results of a phase II study of MAGE-A3, a tumor-specific antigen, also show a nonsignificant "strong signal" in favor of better survival and longer time to relapse, according to Johan Vansteenkiste, M.D., Ph.D., of University Hospital of Louvain in Belgium, and colleagues. The improvements are tending to be similar to those seen with chemotherapy, Dr. Vansteenkiste reported at the European Lung Cancer Conference, although a phase III trial, now underway, is needed to demonstrate efficacy. "Surgical resection is the standard treatment for patients with early stage lung cancer, but after complete resection about 50% will relapse and die from their cancer," Dr. Vansteenkiste said.
He added that post-op chemo improves cure rates, but is "sometimes poorly tolerated by patients recovering from thoracic surgery. In addition, not all patients can withstand chemotherapy."
With MAGE-A3, he said, the reduction in the risk of relapse is currently not significant but is tending to be comparable to that seen with chemotherapy, but with minimal side effects -- mainly injection site reactions and fever over a 24-hour period.
Dr. Vansteenkiste said reactions are similar to those seen with prophylactic vaccines. "That's one of the important things about this approach," he said.
The study included 182 patients, randomized on a two-to-one basis to get either the MAGE-A3 recombinant protein or placebo. The patients were selected to have cancer that expressed the MAGE-A3 protein.
Injections were given over a 27-month period, with the first five given at three-week intervals, then eight given once every three months, the researchers said.
The primary endpoint of the study was disease-free interval, with safety, disease-free survival, overall survival, and assessment of humoral and cellular anti-MAGE-A3 immune response as secondary endpoints.
After a median of 44 weeks of follow-up, Dr. Vansteenkiste and colleagues said:
There were 69 recurrences and 57 deaths.
The disease-free interval hazard ratio was 0.75, with a 95% confidence interval from 0.46 to 1.23, in favor of patients getting the MAGE-A3 protein, although the difference at P=0.127, did not reach significance.
The hazard ratios for disease-free and overall survival were also not significant at 0.76 and 0.81 (also in favor of the MAGE-A3 group) with 95% confidence intervals from 0.48 to 1.21 and 0.47 to 1.40, respectively.
More than 98% of patients given the recombinant protein had an anti-MAGE-A3 IgG antibody response.
T-cell responses were measured in 51 patients and a CD4 T-cell response to MAGE-A3 was seen in 15 of 37 immunized patients (41%), and only in two of 14 patients who got placebo (14%).
Dr. Vansteenkiste said the study was not designed to achieve statistical significance in the efficacy endpoints. "It would be a miracle if, with only 200 patients, you had significance," he said.
Instead, he said, the researchers looked for a "promising signal" that would justify a larger, 2,000-patient phase III trial, which began enrolling patients last year.
The study was sponsored by GlaxoSmithKline the manufacturer of MAGE-A3. Dr. Vansteenkiste reported no conflicts. One of the co-authors is an employee of GlaxoSmithKline Biologicals.
Primary source: European Lung Cancer ConferenceSource reference:Vansteenkiste J, et al "Phase II randomized study of MAGE-A3 immunotherapy as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC): 44-month follow-up, humoral and cellular immune response data" ELCC 2008; Abstract 1480.