Improving Outcomes for Resectable NSCLC
An Emerging Role for Vaccines

This clinical update is based on information presented at a Live Webconference entitled “European Perspectives on Clinical Trials, Clinical Practice, and Treatment Options in Lung Cancer” held on 9 June 2008 in Turin, Italy. The speaker for this topic was Johan Vansteenkiste, MD, PhD from University Hospital Leuven, Respiratory Oncology Unit, Leuven, Belgium. The entire program may be viewed as a webcast at www.primeoncology.org.

Despite complete surgical resection of early stage NSCLC long tern outcomes remain poor. Could vaccines provide an effective immunotherapeutic boost? Ongoing and planned vaccine trials may soon be providing important answers.

Dr. Vansteenkiste pointed out that MAGE-A3 antigen is not expressed by normal cells but is expressed by one-third of NSCLCs. This tumor specificity makes the antigen an excellent target for vaccine therapy and contributes to a favorable toxicity profile. A phase II randomized trial of 182 early stage (pathologic IB or II) patients with MAGE-A3 (+) NSCLC who had complete resection of their disease received either adjuvant MAGE-A3 immunotherapy or placebo postoperatively (Proc ASCO 2007, 25: Abst 7554). The vaccine therapy had an induction phase followed by maintenance (total duration of 27 months). The primary endpoint was disease-free interval following surgery and results favored the vaccine over placebo (HR 0.75, p=0.122). At nearly 5 years post-surgery, vaccine-treated patients OS curve plateaued at 67%, with a trend toward improved survival compared to placebo (p=0.088).The most common side effect was grade 1 or 2 local reactions at the injection sites. Only three grade 3 adverse events possibly related to vaccine therapy were noted.

Based on results of this phase II trial, a new large, global, phase III trial in early stage NSCLC patients (2,270 patients) has been initiated for completely resected MAGE-A3 (+) disease. In the MAGE-A3 (+) as Adjuvant Non-Small Cell LunG CanceR ImmunoTherapy trial (MAGRIT), MAGE-A3 vaccine was given either after standard adjuvant chemotherapy or instead of adjuvant chemotherapy. A decision for chemo vs no chemo is made by patient and physician. If no chemo, then patients are randomized to MAGE-A3 vaccine or placebo. If chemo is chosen, then up to 4 cycles are given followed by randomization to receive either placebo or MAGE-A3 vaccine. The primary endpoint is DFS. This trial is open for recruitment.

Dr. Vansteenkiste stated that other trials are being designed in which MAGE-A3 immunotherapy is being considered for combination therapy either with chemotherapy or targeted agents.

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