Q & A with Elizabeth Mittendorf: A Vaccine to Prevent Recurrence

July 18, 2013 at 5:29 pm 1 comment

Dr. Elizabeth Mittendorf

Dr. Elizabeth Mittendorf

Dr. Elizabeth Mittendorf is leading an international phase III clinical trial that is exploring whether the NeuVax vaccine can reduce the risk of recurrence in women with stage II-IIIa, lymph-node positive, HER2-negative breast cancer. Patients in the trial receive an injection (into the skin) once a month for six months (6 total) and then booster shots every six months for 30 months (5 total).

Q:  How was this vaccine developed?
A: Investigators at MD Anderson found that breast and ovarian cancer cells had an epitope—a part of a molecule the immune system recognizes as foreign—that T-cells were attracted to. Because T-cells are the front line of the immune system’s defense mechanism, this suggested we might be able to develop a vaccine that would augment this process and kill cancer cells.

It took quite awhile to get Neuvax, which is a peptide vaccine, into clinical trials. (A peptide is a sequence of amino acids. You can learn more about peptides and their role in vaccines here. We wanted to use NeuVax in the adjuvant setting, giving it to women who have just completed treatment with the goal of preventing recurrence. Previous peptide vaccine trials tested vaccines in patients who already had metastatic disease (most had metastatic melanoma). Those trials weren’t successful, and we were hoping that using a peptide vaccine in the adjuvant setting would be more effective.

Q: Why would a peptide vaccine not work in the metastatic setting?
A: There are two reasons a peptide vaccine is largely not successful in the metastatic setting. One, a metastatic site is made up of millions of tumor cells, and trying to get the immune system to stimulate enough T-cells to go after millions of tumor cells is difficult. The other reason is that the vaccine does not affect the microenvironment—non-cancerous cells that surround the tumor cells. Some of these cells contain proteins called cytokines that are known to be unfriendly to T-cells.

That said, we are starting to see immunotherapy drugs coming down the pike in metastatic melanoma like ipilimumab (Yervoy). It works by blocking a molecule on T-cells that typically keeps the T-cells from going after cancer cells. This is increasing enthusiasm for immunotherapy. A single peptide vaccine, such as Neuvax, may not be effective for metastatic disease, but it’s possible that a peptide vaccine might be given in combination with other types of immunotherapy to treat metastatic breast cancer.

Q: When did you start the phase I trial?
A: We started the phase I trial back in 2001. The safety data from that study allowed us to role into a phase II study that enrolled approximately 190 patients. The last patients were enrolled in that study in 2007. Our most recent published study on this trial is our 24-month landmark analysis, which showed that the vaccine was clinically effective, but that some patients had a better immune response and what appears to be a trend toward a reduced risk of recurrence than others. These results led to the phase III trial we now have underway.

Q:  Has it been difficult to get women to enroll in this trial?
A: It’s not that difficult to find women. The problem is that there are many other clinical trials that are looking at ways to reduce the risk of recurrence that are enrolling similar patients. Also, we have a very stringent timeline for enrollment. [Women must enroll within 30 days of completing chemotherapy or radiation.]

Q: Could this vaccine also be used to treat DCIS or for breast cancer prevention?
A: If we go to the FDA to seek approval of the vaccine, it would be to treat the same group of women who are enrolled in the trial. So the correct answer would be no. But if investigators can identify through this trial and other trials a biomarker (a biogical marker) that predicts which patients will respond to the vaccine, then it would be possible to do trials investigating the vaccine in patients with DCIS who have that marker. A prevention trial would require a large number of women, take at least 20 years, and be cost prohibitive. That’s the opposite of what we are trying to do now, which is to design sleeker, more efficient trials.

Q: What should women with breast cancer know about the vaccine?
A: I’d like to emphasize that the vaccine is for women who are HER2-negative. I also want women to know that early studies suggest it may reduce the risk of recurrence by 50 percent, and that it’s non-toxic. Women experience some redness at the injection site and some experience some flu-like bone pain, but that goes away. If it’s successful, it will be an important development for HER2-negative patients.

Entry filed under: Vaccines.

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