Blog | Friday, November 11, 2011

QD: News Every Day--Pilot study finds that vaccines benefit metastatic breast, ovarian cancers

Cancer patients seemed to benefit during a pilot study of a cancer vaccine, and the sustained complete response in a patient who remained in the study for more than three years also underscores the potential for therapeutic vaccines.

As the National Cancer Institute explains, cancer vaccines work by activating B cells and killer T cells against cancer. They do this by introducing one or more antigens into the body, usually by injection. Cancer-associated antigens cause B cells and killer T cells to attack those cells.

And, cancer cells may also make much larger amounts of certain self antigens than normal cells. These self antigens may be viewed by the immune system as being foreign and, therefore, may trigger an immune response against the cancer cells.

The latest study represents a tiny trial that suggests a potentially huge strategy, oncologist Elaine Schattner, MD, FACP, commented.

The latest study looked at PANVAC, a recombinant poxviral vaccine expressing the tumor-associated antigens (TAA) carcinoembryonic antigen (CEA) and mucin-1 (MUC-1), and that also included three costimulatory molecules. MUC-1 is a transmembrane glycoprotein that is overexpressed in underglycosylated form in many human carcinoma cells. The cytoplasmic domain of MUC-1 has been shown to play a crucial role in carcinogenesis. CEA is another glycoprotein overexpressed in the majority of adenocarcinomas.

PANVAC also includes transgenes for a triad of human T-cell costimulatory molecules designated TRICOM, composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 3. Such molecules have been shown to generate a stronger immune response and higher numbers of TAA-specific T cells.

This study was a follow-up that looked at PANVAC for metastatic breast cancer or metastatic ovarian cancer, with clinical outcome as the primary endpoint. The first safety study consisted of 25 patients with metastatic gastrointestinal, lung, breast and ovarian malignancies.

Twenty-six patients (12 with breast cancer, 14 with ovarian cancer) were enrolled and given monthly vaccinations. 21 of 26 patients had three or more prior chemotherapy regimens. Results appeared in Clinical Cancer Research.

For the breast cancer patients, median time to progression was 2.5 months (range, 1 to 37+) and median overall survival was 13.7 months. Four patients had stable disease. One patient had a complete response as measured by the Response Evaluation Criteria in Solid Tumors and remained in the study for 37 months, with a significant drop in serum interleukin (IL)-6 and IL-8 by day 71. Another patient with metastatic disease confined to her mediastinum had a 17% reduction in mediastinal mass and remained in the study for 10 months. The authors noted that patients with stable or responding disease had fewer prior therapies and lower tumor marker levels than patients with no evidence of response.

For the ovarian cancer patients, the median time to progression was 2 months (range, 1 to 6) and median overall survival was 15.0 months.

The authors wrote, "Some patients in this study continued to show very good clinical response to subsequent therapies after coming off study. There is accumulating evidence that once a cancer vaccine provokes an immune response in the host, it may initiate a prolonged dynamic process leading to marked responses to subsequent therapies."

They continued that the next step is to consider new endpoints and select patients with less aggressive tumors in the earlier stages of disease. An ongoing randomized study in patients with metastatic breast cancer is comparing PANVAC plus docetaxel to docetaxel alone.