ESMO 2014: Lung Cancer Vaccine Fails to Improve Survival in Surgically Resected Non–Small Cell Lung Cancer
The MAGRIT trial showed disappointing results for a developmental vaccine called MAGE-3 in patients with non–small cell lung cancer (NSCLC) who had undergone surgical resection. This is the largest vaccine trial conducted in lung cancer, and investigators hoped that an immunotherapy approach with a vaccine would improve outcomes. The findings were presented at the ESMO 2014 Congress in Madrid (Abstract 1173O).
At present, about 45% of patients are cured by surgery with or without chemotherapy, and better therapies are needed.
“Vaccinations give us effective soldiers, but in this case they didn’t work on the battlefield,” stated lead author Johan F. Vansteenkiste, MD, Catholic University Leuven, Belgium. He noted that other trials have shown that lung cancer vaccines elicit antibodies and immune cells (ie, “soldiers”) that can kill cancer cells, “but the problem occurs when they come to the battlefield, ie, the environment of the tumor where they are paralyzed by factors in the tumor.”
On the plus side, the MAGE-3 cancer vaccine was well tolerated and the investigational effort identified a predictive marker for treatment benefit—the MAGE-A3 protein. Of the nearly 13,500 NSCLC patients screened for the study, one-third had tumors that expressed MAGE-A3—similar to the expected distribution in NSCLC.
Study Details
MAGRIT was a double-blind, randomized, placebo-controlled study of patients who had undergone complete resection for NSCLC plus or minus chemotherapy prior to randomization.
Of the nearly 13,500 patients’ tumors screened for the presence of MAGE-3 protein, 4,210 were positive. Of these, 2,272 were randomly assigned 2:1 to immunotherapy with the MAGE-3 vaccine and 756 to placebo.
At a median follow-up of 38.8 months, median disease-free survival was 60.5 months in the vaccine group and 57.9 months for the placebo group. About 50% of patients did not receive adjuvant chemotherapy prior to randomization; among this group, median disease-free survival was 58 months and 56.9 months, respectively.
“These results are definitive but disappointing,” Dr. Vansteenkiste said.
About 16% of patients in both treatment arms had grade 3 or higher adverse events, with no significant difference between groups.
Disappointing Findings Elicit Mixed Response
“It is difficult to achieve progress in treating resected lung cancer, and this is one of many failures we have seen in this setting. In the absence of 10 years of progress. we needed to study this. [Patients] had only mild side effects and no patient was harmed. On the plus side, the study provides a detailed database on global treatment patterns,” he said.
For example, in the era of modern thoracic surgery, only 15% of patients in this global trial had whole lung resection. Modern adjuvant chemotherapy was administered in appropriate stages of disease.
Response to the study results was mixed, with MAGRIT investigators believing that the study provides important information that is clinically useful.
“Going forward, the MAGE-3 vaccine may provide benefit if it is combined with immune checkpoint inhibitors that reverse the tumor’s ability to paralyze the immune system [as in ‘releases the brakes from the immune system’]. New formulations of vaccines may also perform better [than MAGE-3],” Dr. Vansteenkiste said.
Martin Reck, MD, PhD, of Hospital Grosshansdorf, Germany, said that the concept of vaccination in lung cancer is questionable and other immunotherapeutic approaches, including checkpoint inhibition, should be pursued.
GlaxoSmithKline, the company that is developing the vaccine, attempted to identify a subgroup of patients who benefitted, but no subgroup could be identified. The vaccine remains under development for melanoma, but no other studies are planned in lung cancer.
For full disclosures of the study authors, view the study abstract at www.esmo.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
