SAN ANTONIO, TX (Ivanhoe Newswire) - Conquering breast cancer is not an easy feat. Once it's beaten, there's always a chance it could come back. Now doctors are working on a new way to help breast cancer survivors win the fight once and for all.
Kellie Trombitas is a fighter. It took 33 roundsof radiation for her to knock-out breast cancer over 10 tough months.
"Chemo takes a lot out of you. It just makes you sick," Kellie Trombitas told Ivanhoe.
Now she's excited to be cancer free, but Kellie still has concerns.
"In the back of your mind you're always thinking, is it going to come back?" Kellie said.
So she's taking part in a clinical trial to test E-75, a vaccine to help protect breast cancer survivors from recurrence.
E-75 is a part of the Her-2 neu protein. It helps stimulate t-cells to attack cancer cells. In trials, women injected with the vaccine saw a 50% reduction in recurrence. The drug Herceptin can do the same but in a different way. Only 20% of breast cancer survivors, those with high levels of Her-2, can take Herceptin.E-75 developer George Peoples says three times as many survivors could benefit from his vaccine. It targets women like Kellie, who havelower levels of Her-2.
"It allows us to use the vaccine for patients who are otherwise not eligible to receive Herceptin," George E. Peoples, M.D., FACS, director of the Cancer Vaccine Development Program and chief surgical oncology at SAMMC, said.
As for Kellie, she's still getting stronger, fighting to keep cancer from making a comeback.
Doctor Peoples said one day the vaccine could be used to fight lung, prostate and ovarian cancers that also express the Her-2 protein. Recruiting for the final round of trials for E-75 is underway right now.
Seven hundred to 1,000 participants in dozens of sites across the country are needed. To find out more about enrolling in the trial go to www.neuvax.com.
BACKGROUND: According to U.S. cancer statistics, 1 in 8 women will develop invasive breast cancer over the course of her lifetime. In 2011, an estimated 230,480 new cases of invasive breast cancer were expected to be diagnosed in women in the U.S., along with 57,650 new cases of non-invasive breast cancer. Breast cancer is the second most common diagnosed cancer among American women. (Source: www.breastcancer.org).
RISK FACTORS: A woman's risk of breast cancer increases by nearly half if she has an immediate family member who has been diagnosed with breast cancer. About 15% of women who get breast cancer have a family member diagnosed with it. About 5-10% of breast cancers can be linked to gene mutations inherited from one's mother or father. Mutations of the BRCA1 and BRCA2 genes are the most common. Women with these mutations have up to an 80% risk of developing breast cancer during their lifetime, and they are more likely to be diagnosed at a younger age (pre-menopause). (Source: www.breastcancer.org).
TREATMENT AND RECURRENCE: Breast cancer treatments can be local or systemic. Treatments include; surgery, radiation therapy, chemotherapy, hormone therapy, and biological therapy such as Herceptin. Herceptin works by using the body's own immune system to destroy cancer cells. Herceptin targets breast cancer cells that have high levels of a protein called HER2. Amplification or over-expression of the ERBB2 gene occurs in approximately 30% of breast cancers. It is strongly associated with increased disease recurrence and a worse prognosis. HER2 proteins have been shown to form clusters in cell membranes that may play a role in tumorigenesis. Recurrent breast cancer is breast cancer that comes back after initial treatment. Although treatment is aimed at eliminating all cancer cells, a few may survive. These undetected cancer cells multiply, becoming recurrent breast cancer. It may occur months or years after your initial treatment. (Source: webmd.com, mayoclinic).
NEW TREATMENT: NeuVax E-75 is a vaccine given as supplementary therapy to prevent disease recurrence. NeuVax consists of the E-75 peptide derived from human epidermal growth factor receptor 2 (HER2) combined with the immune adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF). Treatment with NeuVax stimulates cytotoxic (CD8+) T cells in a highly definitive approach to target cells expressing any level of HER2. NeuVax is given as an intradermal injection once a month for six months, followed by a booster injection once every six months. Based on a successful Phase 2 trial, which achieved its primary endpoint of disease-free survival (DFS), the Food and Drug Administration (FDA) granted NeuVax a Special Protocol Assessment (SPA) for its Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) study. A Phase 3 trial is expected to begin in the first half of 2012. (Source: www.globenewswire.com).
Dr. George Peoples, Director of the Cancer Vaccine Development Program and Chief of Surgical Oncology at San Antonio Military Medical Center (SAMMC), talks about what's helping women who've fought breast cancer once, from fighting it again.
What is E75?
Dr. George Peoples: E75 is actually a piece of the HER2/neu protein which is only expressed in large amounts on cancer cells. This peptide happens to be a very important piece because it is the point of recognition for the immune system. Killer T-cells that fight disease, recognize these small pieces of proteins that are presented to them by HLA molecules. That combination of HLA molecule and peptide is what stimulates the killer T-cells to do their job which is to kill that cell. E75 is that peptide or piece of a protein that is most recognizable to the immune system on certain cancer cells.
How does it work?
Dr.George Peoples: This researchhas been going on a long time and traces back to the idea that the immune system can in fact recognize and kill cancer cells. Once that concept became fairly well established, we began to look at the mechanism behind it. We began the search for the antigen that was being recognized and more importantly for the the piece of the protein that was most antigenic or recognizeable to the immune system. That work was all done in the 90's, andE75 was originally described in 1995. We began working with this peptide shortly thereafter and began to turn this peptide into a vaccine. The idea was to use the E75 peptide with an immune stimulant together as a vaccine (now named NeuVax) to generate a robust response to get T-cells revved up and able to recognize and kill cancer cells. Once the vaccine had been validated in preclinical studies, we began the clinical process. The clinical testing process began with a phase I trial, which looked for the safety of using the vaccine and also the appropriate dosing of the peptide in order to get the most optimal immune response. Once we figured out the safety and dosing, then we began phase II which determines whether the vaccine can be clinically effective. That's when we began to treat women to determine whether or not we could actually prevent recurrences of their cancer.
So how confident are you from what you've seen in phase II and phase III that this will get approval?
Dr.George Peoples: If we see in the phase III trial what we saw in phase II, it will get approved, but that's always the big question. We see a lot of promising phase II drugs that don't do as well as in phase III, and a lot of times it's because of the added features of phase III trials that make them so much more stringent.
What did you see in phase II?
Dr. George Peoples: In phase II, we actually had about 200 women with approximately half vaccinated and half followed prospectively as our control arm. Those women that were vaccinated had their vaccinations done once a month over six months. About half of those women went on to receive also booster inoculations that was a component of the trial that was added a little bit later. But all of the women both vaccinated, boosted and not boosted, as well as the control group were followed for 5 years. The last woman actually will complete her 5 year follow up this summer and that trial will be officially closed. What we have up to this point, pending the last few follow-ups, is about 20% recurrence rate in the control group and about a 10% recurrence rate in the vaccine group, so about a 50% reduction in overall recurrences.
That's a pretty substantial number correct?
George Peoples: It is a substantial number. A lot of times when you hear about new chemotherapies or new regimens and new combinations of drugs being tested, they get approved based on a 10% improvement and here we saw a 50% improvement. We're shooting for a substantial number in the phase III trial as well; it's a reduction in recurrence by a third. So we've backed off of the 50% a little bit to try to make it a bit of an easier target to hit and increase the chances of the phase III being successful.
What is the normal recurrence rate right now?
Dr.George Peoples: The recurrence rate is based on the stage of the disease. Typically, we look at women as being node positive or node negative just as a general guide. Women who are node positive, which is the patient population that's being targeted in the phase III trial, their risk of recurrence is somewhere around 20 and 25% at 3 years.
So why not just vaccinate every woman with NeuVax?
Dr. George Peoples: We'd love to get there, but we have to answer some key questions first. One of the issues will be whether or not this particular vaccine is going to be "the right vaccine" for using as a truly preventive vaccine. Another problem with prevention trials overall is that they take a long time to conduct. For example, I can take a group of women who have a known risk for breast cancer and vaccinate them, but it could be 20 years before a woman who is at risk actually develops the disease. So, it could take a very long time before I would know if I benefited anyone with the vaccine. So, we have tried to take vaccines into what we think is the appropriate setting which is to prevent disease, but to test in a group of people that we have some defined numbers around as far as the risk of recurrence and probably even more importantly time to recurrence. The group that I mentioned previously, the node positive women, we know that their risk is 20-25% and we know that rate is at 3 years. So, thatgives us a timeframe in which we can actually test a vaccine in a reasonable period. While it's not primary prevention, it is prevention.
What makes you excited about this trial?
Dr.George Peoples: I think what is very exciting is the vaccine targets a protein called HER2/neu. Now HER2/neu became very famous because of Herceptin, a very popular and successful breast cancer drug that targets this same protein. The mechanism of action between the way Herceptin targets HER2/neu and the vaccine targets HER2/neu are very different , and as a result of that, it allows us to use the vaccine in patients who are otherwise not eligible to receive Herceptin. Even beyond that, the thing that really excites me about this is there are a lot of different cancers that express HER2/neu. Now we really don't think about HER2 expression in them because they do not have that highest level of expression necessary for Herceptin use, but other cancers that come from an epithelial cell origin like all the most common cancers: lung cancer, colon cancer, prostate cancer, ovarian cancer do express some level of HER2/neu. Just as we target the 1+ and 2+ levels in breast cancer, theoretically those other cancers may be targetable as well because they do express HER2/neuat the 1+ and 2+ level.
What is that 60% vs. 20%?
Dr. George Peoples: That's correct. If you look at all of breast cancer, the majority of them will actually express HER2/neu, but at different levels. In fact, the way it works out only about 20% of women will have that highest level of HER2/neu expression or over expression which is required to be eligible for Herceptin. If only 20% have that highest level and about 20% have zero or no level, that leaves that middle 60% that have low to intermediate or 1+ to 2+ levels of HER2 expression. That's the group that's being targeted in this E75 phase III trial.
If it got FDA approved for breast cancer, could doctors use it to see if it was effective with t other types of cancer?
Dr. George Peoples: Well it should be studied in more trials. A lot of things do happen and people do use things off label but what would be most appropriate is if it appears to work, and work well, then immediately we should begin trials on all these other different types of cancers. Herceptin has spread past breast cancer, and it's now approved in gastric cancer, for example. Unfortunately, only about 10% of gastric cancers have that high level of expression required and the other cancers that I mentioned have an even lower percentage of high HER2 expression. . If the phase III is successful, then there will be that immediate desire to start testing these other cancers which do have low to intermediate HER2 expression.
What's the timeframe of phase III?
Dr. George Peoples: The primary endpoint of the trial is 3 year disease-free survival. Every patient being enrolled to that trial will be followed for a minimum for 3 years to meet this endpoint. The trial will likely take approximately 18 months to enroll, so the entire trial will be approximately 4.5 years.
How can people enroll in this trial?
Dr. George Peoples: They're two different sites that have all the information available. They can go to www.neuvax.com to find out more information about the vaccine and trial or they can go to the trial sponsor's website at www.galenabiopharma.com.
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