Jan 12, 2015
By Shira Klapper, Senior Writer/Editor
A study showing that immunotherapy can confer a possible survival advantage in patients with pancreatic cancer was published in the Journal of Clinical Oncology (JCO), online, ahead of print, January 12, 2015. The study, “Safety and Survival with GVAX Pancreas and Listeria Monocytogenes-Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer,” was carried out across 10 U.S. cancer centers.
The phase II study found that patients who received the immunotherapy GVAX—which is administered with cyclophosphamide—plus immunotherapy CRS-207 had a significantly longer overall survival (OS) of 6.1 months, compared to an OS of 3.9 month among patients who received GVAX alone, translating into a 56% improvement. The study also found that patients who produced mesothelin-specific CD8 T cells (tumor specific T cells) as a result of treatment also had a longer OS, regardless of whether those patients received the combination treatment or GVAX alone.
GVAX is a cancer treatment composed of pancreatic cancer cells that have been genetically engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates the immune system to produce T cells. CRS-207 is a vaccine composed of genetically modified listeria monocytogenes that serve to stimulate an immune response against the protein mesothelin on pancreatic tumor cells. Mesothelin is an antigen that is over-expressed in most pancreatic ductal adenocarcinomas (PDA).
Commenting on the study’s findings, study first author, Dung T. Le, MD, said, “I think the most exciting finding is that a disease that’s not particularly thought to be responsive to immunotherapy might be responsive to this combination strategy.”
A “prime” and a “boost” confer a survival advantage
The current study was based on a phase I study that assessed the safety of CRS-207.
“What we noted in that previous study was that the patients with pancreatic cancer who did the best were the patients who had come from prior GVAX studies,” said Dr. Le. In other words, patients did best when GVAX was given first and acted as the “prime” for treatment, followed by CRS-207, which acted as the “boost” for the immune response. This is also true in mouse models of cancer.
Previous studies also showed that administering cyclophosphamide the day before GVAX helped to suppress regulatory T cells, thus improving immune response.
The study randomly assigned 61 patients into the GVAX/CRS-207 arm to receive two doses of cyclophosphamide followed by GVAX followed by four doses of CRS-207 every three weeks. The 29 patients in the second arm received six doses of cyclophosphamide /GVAX alone every three weeks. The most frequent adverse events were erythema (77% of patients), induration (71%), pain (62%), and pruritus (71%).
A basis for future studies on immunotherapy in pancreatic cancer
Looking ahead, this study will hopefully serve as the basis for future studies examining how patients with PDA respond to the effects of GVAX and CRS-207, either alone or in combination with other therapies. Additional studies are already under way to compare the combined GVAX/CRS-207 to chemotherapy and to CRS-207 alone.
Dung Le, MD, is an assistant professor at the Johns Hopkins Kimmel Cancer Center. An ASCO member since 2006, she has received a Conquer Cancer Foundation of ASCO 2008 Career Development Award (CDA) and is a member of the Conquer Cancer Foundation Grants Selection Committee.*
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Le DT, Wang-Gillam A, Picozzi V, et al. Safety and survival with GVAX pancreas and listeria monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. Epub 2015 Jan 12.
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@ 2014 American Society of Clinical Oncology