IMMUNOTHERAPY FOR PANCREATIC CANCER

An immunologic one-two punch significantly improved overall survival and doubled the probability of one-year survival for patients with previously treated, metastatic pancreatic ductal adenocarcinoma.

The combination of an irradiated, whole-cell tumor vaccine (CY/GVAX) and an immunostimulant vaccine containing live, attenuated Listeria monocytogenes bacteria (CRS-207) was associated with a median overall survival of 6.1 months, compared with 3.9 months for patients treated with CY/GVAX alone.

The one-year survival rate for patients treated with the combination was 24%, compared with 12% for patients treated with CY/GVAX only.The study was stopped at the first interim analysis because of the statistical superiority of the combined vaccines, which were then offered to all patients, said lead author Dung T. Le, MD, an assistant professor of medicine at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.

Dr. Le spoke at a teleconference press briefing held in advance of the 2014 Gastrointestinal Cancers Symposium.

"These are exciting results in a poor-prognosis cancer," said Smitha S. Krishnamurthi, MD, associate professor of medicine at Case Western Reserve University in Cleveland, Ohio, who was not involved in the study.

"This is a phase 2 study, but it is the first randomized study in metastatic pancreatic cancer demonstrating an improvement in survival. Patients who received at least one dose of the CRS-207 vaccine had a doubling of survival, and this was accomplished without the side effects of chemotherapy," said Dr. Krishnamurthi, who moderated the symposium teleconference.

The GI Cancers Symposium is cosponsored by the American Gastroenterological Association Institute, the American Society of Clinical Oncology^® (ASCO), the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Per-Protocol Survival Even Better

The combined immunotherapy approach is designed to attack cancer cells on two major fronts simultaneously.

The CY/GVAX consists of irradiated granulocyte macrophage colony-stimulating factor–secreting allogeneic cell lines delivered intradermally to evoke an antigenic response from the immune system. Prior to administration, patients receive low-dose cyclophosphamide to suppress regulatory T cells that may interfere with the desired response.

CRS-207 contains live but weakened L. monocytogenes, which express mesothelin, a protein that is also overexpressed on most pancreatic cancer cells. The bacteria-based vaccine triggers potent activation of innate and antigen-specific immune responses, Dr. Le explained.

In the phase 2, open-label trial, patients with metastatic pancreatic cancer who failed or refused chemotherapy were randomly assigned on a 2:1 basis to 2 doses of CY/GVAX 3 weeks apart, followed by 4 doses of CRS-207, also every 3 weeks (60 patients), or 6 doses of CY/GVAX every 3 weeks (30 patients). Patients who were clinically stable could repeat the courses.

Dr. Le presented data from two analyses: a full data set containing information on all patients who received at least 1 dose of treatment, and a per-protocol analysis of patients who received at least 3 doses of immunotherapy, which was about 70% of the study population.

In the per-protocol analysis (patients who received at least 3 doses) median overall survival was 9.7 months compared with 4.6 months (2-side log rank P = .0335).

This outcome compares favorably with the survival findings from the full patient population who had 1 or more doses of treatment.

The vaccines appeared to be safe and well tolerated. The primary adverse events associated with CY/GVAX were transient local infusion reactions, and with CRS-207 were transient fevers and chills that can be managed with medication, Dr. Le said in response to a question from Medscape Medical News.

The vaccine combination is currently being investigated in a clinical study comparing it with both CRS-207 alone and chemotherapy alone.

The trial was sponsored by Aduro Biotech. Dr. Le reported no relevant conficts of interest. Many of her coauthors are employees and/or stockholders in the company. Dr. Krishnamurthi reported no relevant conflicts of interest.