The gist: Cancer vaccines are a form of immunotherapy—treatment meant to boost a patient’s own immune system to fight cancer. Unfortunately, they have not proven very successful when tested in lung cancer patients in clinical trials. The disappointing trend continues with new results from a clinical trial testing a vaccine called MAGE-A3. However, we posted a story yesterday about scientists’ hopes that cancer vaccines may start working better when paired with certain drugs called checkpoint inhibitors.
“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.”
“Using vaccines to fight cancer is a field littered with failures but experts believe it is possible the approach could get a new lease of life if such shots are combined with a new class of drugs called checkpoint inhibitors.
“Unlike traditional preventative vaccines, therapeutic cancer vaccines are designed for people with established disease and are supposed to boost the patient’s immune system to keep tumors at bay.
“Unfortunately, the theory has not worked out in practice because, while the vaccines are successful at triggering a response from the ‘foot soldiers’ of the immune system, cancer cells still manage to escape detection.
“The result has been a series of failures with high-profile experimental cancer vaccines such as Merck KGaA’s Stimuvax and GlaxoSmithKline’s MAGE-A3.
“GSK threw in the towel on its vaccine in April, dashing hopes for a project that was once seen as a potential multibillion-dollar sales opportunity in lung cancer and melanoma.”
“GlaxoSmithKline has been forced to halt a Phase III trial assessing its MAGE-A3 cancer immunotherapeutic in patients with non-small cell lung cancer (NSCLC).
“High hopes for the experimental immunotherapy – designed to help patients stave off the return of the disease after treatment – came after it emerged that researchers would not be able to identify a subset of patients who may benefit from its therapy, hot on the heels of other disappointing data.”
Editor’s note: Immunotherapy drugs are meant to boost a patient’s own immune system to fight cancer. We previously posted about the immunotherapy drug MAGE-A3. Even though it did not perform very well when tested in a clinical trial, researchers hoped to find a subset of patients who could benefit. However, it seems they could not.
“GlaxoSmithKline plc (LSE:GSK) today announced that analysis of the MAGRITi trial, a phase III trial of its MAGE-A3 cancer immunotherapeuticii in non-small cell lung cancer (NSCLC) patients, showed that the trial did not meet its first or second co-primary endpoint as it did not significantly extend disease-free survival (DFSiii) when compared to placebo in either the overall MAGE-A3 positive population (first co-primary endpoint) or in those MAGE-A3-positive patients who did not receive chemotherapy (second co-primary endpoint). GSK currently remains blinded to the overall trial data from the analysis of the first two co-primary endpoints to allow for the unbiased generation of a mathematical model to assess the third co-primary endpointiv.”
Editor’s note: This story is about a drug that is meant to boost the patient’s own immune system to fight lung cancer. The study has found no significant survival benefit of the drug, but the drug company hopes to find a sub-population of people with lung cancer for whom the drug will work. Learn more about immunotherapy and clinical trials.
In the past 2 years, cancer treatments known as immune therapies have become all the rage. However, they have actually been explored for decades, particularly in melanoma, and have produced some notable successes. Now, immune therapies are showing more and more promise for lung cancer. Continue reading…
New results from an ongoing clinical trial suggest that an experimental vaccine may not keep melanomas from coming back after all. The vaccine targets tumors that express a gene called MAGE-A3, which is active in 65% of melanomas that have begun to spread. However, researchers will continue the phase III trial because even though this treatment does not work on melanomas broadly, it could still control a tumor subtype with a particular mutation. The results of the continued study are expected in 2015. In addition, the MAGE-A3 vaccine is being tested against non-small cell lung cancer in another phase III trial, and initial findings are expected in 2014.
Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, et al. J Clin Oncol. May 28, 2013.
The MAGE-A3 protein is expressed in approximately 35% of patients with resectable non–small-cell lung cancer (NSCLC). Several immunization approaches against the MAGE-A3 antigen have shown few, but often long-lasting, clinical responses in patients with metastatic melanoma.
A double-blind, randomized, placebo-controlled phase II study was performed assessing clinical activity, immunologic response, and safety following immunization with recombinant MAGE-A3 protein.
In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.
Ulloa-Montoya F, Louahed J, Dizier B, Gruselle O, et al. Journal of Clinical Oncology. Jul 1, 2013.
“To detect a pretreatment gene expression signature (GS) predictive of response to MAGE-A3 immunotherapeutic in patients with metastatic melanoma and to investigate its applicability in a different cancer setting (adjuvant therapy of resected early-stage non–small-cell lung cancer [NSCLC]).”
Kruit WH, Suciu S, Dreno B, Mortier L, et al. J Clin Oncol. May 28, 2013.
“Active immunization against the tumor-specific MAGE-A3 antigen is followed by a few but impressive and durable clinical responses. This randomized phase II trial evaluated two different immunostimulants combined with the MAGE-A3 protein to investigate whether a more robust and persistent immune response could be associated with increased clinical benefit.”