Metastatic pancreatic cancer treatment promise offered by vaccines

15/1/2014

Metastatic pancreatic ductal adenocarcinoma patients treated with two different anti-cancer vaccines had improved survival compared to treatment with only one of them.

The anti-cancer vaccines used in this randomised phase 2 trial were GVAX Pancreas followed by CRS-207, and the comparison was made against treatment with GVAX alone.

The greatest differences were seen in patients who received at least two doses of GVAX and at least one dose of CRS-207 and in those who received two or more prior treatment regimens.

“This is the first time a randomised study has shown that immunotherapy is effective in pancreatic cancer. This study is just a first step, and we believe we’ll be able to take this approach further,” said lead study author Dung T. Le, MD, an assistant professor of medicine at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore, Md. “Various chemotherapy drugs are used, but there are no standard treatment options for second- or third-line therapy in this setting. We’re excited these patients may soon have an alternative to chemotherapy that could come with fewer side effects.”

Advanced pancreatic cancer has a very poor prognosis.

The best reported median survival of 11 months comes from first-line treatment with the chemotherapy regimen FOLFIRINOX. However, due to its side effects, only the fittest patients qualify for this treatment, and reported survival with other chemotherapy regimens is lower.

For patients whose disease progresses despite first-line treatment, the median survival ranges from four to six months with second-line therapy, and two to four months with third-line therapy.

The present study tested an innovative immunotherapy strategy that promises to improve outcomes for such patients and appears to be better tolerated than chemotherapy. The GVAX vaccine is composed of pancreatic cancer cells that have been genetically modified to secrete a protein called GM-CSF, which stimulates the immune system.

The vaccine is given with a low-dose of a common cancer drug called cyclophosphamide to boost the effectiveness of the vaccine. The second vaccine, CRS-207, is a form of the bacterium Listeria monocytogenes that has been genetically modified to be safe for human use, while retaining its ability to stimulate the immune system.

Specifically, CRS-207 has been engineered to stimulate an immune response against the protein mesothelin, which is present at high levels on pancreatic cancer cells. The combination of the two vaccines intends to stimulate an immune response against pancreas tumor cells, first with GVAX inducing a broad response against multiple tumor proteins and then with CRS-207 boosting immune response against the mesothelin protein. Essentially, this combinatorial vaccination approach enhances the patients’ natural immune system and trains it to recognise and attack pancreatic tumors.

Ninety patients with metastatic PDAC, the most common form of pancreatic cancer, were enrolled in the study and randomly assigned to treatment with GVAX followed by CRS-207 (arm A) or GVAX alone (arm B). Nearly all patients had previously received at least one prior course of chemotherapy.

At a planned interim analysis of the study, the median overall survival was significantly longer with the two-vaccine therapy compared to GVAX alone (6.1 months vs. 3.9 months). About 24% of patients in arm A were still alive after one year, compared with 12% in arm B. Among patients who received at least three doses of vaccine (about 70% of all patients), those in arm A who received 2 doses of GVAX and at least one dose of CRS-207 had a median overall survival of 9.7 months compared to 4.6 months with GVAX alone. Based on the benefit observed at this interim analysis, patients were allowed to cross over from arm B to arm A. The side effects of the vaccine were relatively mild, resolved quickly, and did not get worse with each dose of treatment (as is often the case with chemotherapy).

The GVAX/CRS-207 combination is one of several related immunotherapy strategies under clinical investigation. The researchers are about to open a large phase 2 study that will compare the vaccine combination versus CRS-207 alone versus chemotherapy as second-line or greater therapy for metastatic pancreatic cancer. They are also looking at combining GVAX/CRS-207 with immune checkpoint inhibitors such as ipilimumab and anti-PD-1/PD-L1. A study testing GVAX/ipilimumab as a maintenance treatment for patients whose disease became stable on FOLFIRINOX has recently opened.

 

Source: eCancer News: http://ecancer.org/news/5100-asco-gi--study-identifies-a-promising-vaccine-combination-for-patients-with-metastatic-cancer-of-the-pancreas.php

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