SAN ANTONIO, – Military researchers here are testing a cutting-edge breast cancer vaccine to cut recurrence rates and giving some survivors a better shot at a cancer-free future.
After more than a decade of research and testing, the cancer vaccine, dubbed E-75, soon will move on to its final phase of testing to earn Food and Drug Administration approval, said Army Col. (Dr.) George E. Peoples, director and principal investigator for the Cancer Vaccine Development Program at San Antonio Military Medical Center.
The team has high hopes for this vaccine and its lifesaving potential for breast cancer survivors, particularly since breast cancer is the most prevalent type of cancer seen among military beneficiaries in the hospital here, said Peoples, who also serves as the deputy director of the U.S. Military Cancer Institute and the medical center’s chief of surgical oncology.
“We’ve made a commitment to take care of active-duty personnel, spouses and retirees,” the colonel said. “And cancer is a notable problem among beneficiaries.”
The vaccine, Peoples explained, targets a protein commonly over-expressed in breast cancer cells called human epidermal growth factor receptor 2, or HER2/neu.
Cancer vaccines typically target some protein or antigen expressed on cancer cells, he noted. “The idea is to train the immune system to recognize that protein or piece of protein that’s highly expressed on cancer cells, but not on normal cells,” he said. “That way the immune system can differentiate what’s abnormal and normal. If the immune system can recognize it, it marks it for death, basically.”
The cancer vaccine concept has been around for a long time, Peoples noted, but the team here has adopted a different approach to test their effectiveness. The vast majority of vaccines in the past were tested on end-stage cancer patients, he explained. However, a vaccine is meant to stimulate the immune system, and a healthy immune system isn’t typically seen in someone in the last stages of cancer.
As a result, “a lot of early cancer vaccines tested … in end-stage patients were found not to be helpful,” Peoples said. “No real surprise there.”
To more appropriately gauge the vaccine’s effectiveness, Peoples’ team decided to test it among patients who have a healthy immune system -- cancer survivors who are disease-free but at risk for recurrence. Experts can predict recurrence based on several factors including family history, age, size of tumor and the presence of involved lymph nodes, among other indicators.
The researchers targeted the HER2/neu protein, which is expressed at varying levels in women with breast cancer, then honed in on the 60 percent of women who express the protein at low to intermediate levels. The vaccine is a mix of the E-75 peptide of the HER2 protein and an immune system stimulant.
They started with a 200-patient trial in 2001 and followed each woman for five years. Half of the women received the vaccine -- one injection a month for six months -- and the other half was the control group.
The outcome was very promising, Peoples noted. The recurrence rate among the women in the control group was 20 percent, and 10 percent among the women who received the vaccine. “We cut recurrence in half,” he said.
This success led to the next phase of testing, the colonel said, which will begin early this year and involve 700 to 1,000 patients.
Unlike the earlier phases, however, this step will be undertaken by a commercial company, Galena Biopharma, which has the resources and manpower to undertake such a large-scale test. The company will seek FDA approval and, if received, release the vaccine for public use.
This phase will take about five years to complete -- two years to enroll, then a three-year observation period, Peoples said.
“The end point is the recurrence rate after three years,” he explained.
Meanwhile, Peoples and his team will turn their attention to a multitude of other projects, many based on the same concept that made the E-75 vaccine so successful -- using the body’s own immune system to destroy cancer cells.
They’ve already taken the same vaccine and completed a trial with prostate cancer survivors. As with ovarian and lung cancer, prostate cancer also expresses the HER2 protein.
Peoples said he’s also intrigued by a successful trial they conducted on breast cancer survivors who express the HER2 protein at the highest levels, rather than the low to intermediate levels they focused on before. In this study, they combined their vaccine with the drug Herceptin.
They conducted a small trial with 60 women, Peoples said, and when they administered the vaccine and Herceptin together, the recurrence rate dropped to zero. “The preliminary data is very exciting,” he said. “But we need to wait and do larger trials.”
He praised the military men and women willing to take part in the trials. They enter into them knowing they may be part of the control group that doesn’t receive a potentially lifesaving vaccine. Despite that fact, he hasn’t seen a shortage of willing participants, Peoples said.
“The military is an ideal setting for clinical trials,” he said. Service members, retirees and family members have a strong sense of service, he noted. “They want to be involved and contribute to the research,” he added.
While they’re focusing on secondary cancer prevention, the ultimate goal, Peoples noted, is primary prevention, meaning cancer prevention among people with a predicted risk of cancer based on family history and genetic markers. “Hopefully, sometime in my lifetime we’ll figure that out,” he said.
Please read an Important Update: http://www.army.mil/article/78062/
Another recent update: http://www.army.mil/article/89790/ and read below:
E75 PHASE II CLINICAL TRIALS COMPLETE
Sept. 10 was a key date for the CVDP: Phase II of a clinical trial on a peptide called E75 concluded after eleven years. E75 was discovered in the mid-1990s, and Peoples has taken it through consecutive stages of development -- pre-clinical, clinical and human trials. Phase II of the trial studied E75 in preventing recurrence of breast cancer in a control group of cancer survivors vs. a vaccinated group. The final Phase II report will be delivered at the San Antonio Breast Cancer Symposium in December.
A Phase III trial began in January and will include between 700 and 1,000 breast cancer patients around the world.
"The Phase II trial data has shown that the rate of breast cancer recurrence in women who received E75 was half the rate observed in the control group," said Peoples. "We look forward to seeing if the Phase III trial will confirm these results."
E75 IN COMBINATION WITH TRASTUZUMAB (HERCEPTIN)
This fall Peoples hopes to initiate a new clinical trial at the CDVP that uses the E75 vaccine in combination with trastuzumab (Herceptin), an injection currently used to treat breast cancer, to test for a synergistic effect. Breast cancer patients who express a high level of HER2/neu are indicated for treatment with Herceptin. This study examines whether vaccine therapy combined with Herceptin may be an option for those with lower or moderate rates of HER2/neu expression.
AE37 STUDY PRESENTED AT AMERICAN COLLEGE OF SURGEONS CLINICAL CONGRESS
On Oct. 2 at the American College of Surgeons Clinical Congress, the CDVP presented a poster on another peptide, AE37, which showed that after completing standard treatment, breast cancer survivors who received injections of AE37 were more likely to survive in remission without recurrence than the control group in the study. While AE37 did not prevent recurrence in all patients, it provoked an immunologic response in patients across the board, including survivors at high risk of recurrence, those with the hard-to-treat "triple negative" form of breast cancer and those with lower levels of HER2 expression.
"Patients with a lower level of expressed HER2 protein, who wouldn't be eligible for the HER2-binding antibody, trastuzumab (Herceptin), had a survival rate of more than 88 percent, compared to 70 percent in the control group," said Capt. John Berry, MD, a research associate. "The vaccine may have benefited patients with less aggressive cancers."
E39 TARGETS A NEW PROTEIN
The first patient was enrolled in August of this year as the CVDP moves into an exciting new direction with a new series of trials on a vaccine peptide (E39) that targets a different highly expressed protein, FBP -- an abbreviation for folate binding protein -- instead of HER2. There are no drugs currently available that target FBP.
A major innovation of the CVDP was its emphasis on reducing recurrence in breast cancer survivors that successfully completed a course of standard treatment prior to being vaccinated.
"Our program was one of the first to enroll cancer survivors with healthy immune systems rather than focus on people with end-stage, metastatic cancer," said Peoples. "Enrolling patients with very advanced cancer is a holdover from trials testing toxic chemotherapies. Data has shown that the vaccines, in contrast, are non-toxic."
In the meantime, cancer remains a major threat to human health and Peoples saaid there is much work ahead for the CVDP.
"The ultimate goal is to vaccinate at-risk patients who have never had cancer," he said. "We are looking at areas of future research in combining vaccines and combining a vaccine with other forms of immunotherapy. HER2/neu is expressed in other cancers, and we hope to one day have vaccines to prevent lung, colon, prostate and ovarian cancers."
Peoples received his undergraduate degree from the United States Military Academy at West Point, N.Y., in 1984 and graduated from Johns Hopkins School of Medicine. His interest in immunotherapy and cancer research was sparked during his residency in general surgery at Brigham and Women's Hospital in Boston. He continued his education with a research fellowship at the Laboratory of Biologic Cancer Therapy at Harvard Medical School, and training in surgical oncology at MD Anderson Cancer Center. He has been working on cancer research ever since.
Update January 18, 2014. In a telephone conversation with Drs. Peoples and Shumway of the Cancer Vaccine Development Program, it was learned that Dr. Peoples is in the process of retiring from the military and being replaced by Dr. Nathan Shumway, who will continue the research project with trials through the VA system. Dr. Peoples will continue with civilian trials.
Important update on 2 new drugs that received FDA approval, please read
April 3, 2014 update: The funds we donate are being used to support this Phase II breast cancer vaccine study that is ongoing at over a dozen sites. However, due to confidentiality provisions in agreements we are unable to mention the specific compounds being used. The medications now used in combination are different and more advanced than the E-75 peptide. Our donations will add staff and
Thank you, Mr. Norman R. Gardner, Director of Clinical Trials for providing us with this update.
March 22, 2015 update: GP2 is a new drug that is being used in research by the Anderson Cancer researchers, and is likely being used in the cocktail of medicines involved in our study, however confidentiality agreements prevent this from being disclosed. Some of the drug manufacturers are involved in licensing litigation, concerning ownership of the new vaccines, and we are monitoring the arbitration and appeal with the hope that a vaccine can be sped to market and the issues involved can be promptly resolved in an amicable manner; the over-riding consideration should be saving lives and not which drug manufacturer can profit the most in the end. (editor's comments)
September 6, 2016 update:
The protocol is still ongoing, however, the enrollment has been met. Patient are still on follow up though and will be for some time. Dr. Peoples and Dr. Shumway have retired from the Military and Maj. Kuang Chang, MD is the new PI. Thank you Mr. Norman R. Gardner, Director of Clinical Trials, for this update.
Chemotherapies: Because advanced breast cancers are often hard to treat, researchers are looking for newer drugs.
A drug has been developed that targets cancers caused by BRCA mutations. It is in a class of drugs called PARP inhibitors and is called olaparib. It was successful in treating breast, ovarian, and prostate cancers that had spread and were resistant to other treatments. Further studies are under way to see if this drug can help patients withoutBRCA mutations.
Targeted therapies are a group of newer drugs that specifically take advantage of gene changes in cells that cause cancer.
Drugs that target HER2: Recently, a new drug for patients whose cancer cells have too much HER2 protein has been approved by the FDA. This drug, ado-trastuzumab emtansine (Kadcyla™) was formerly called TDM-1. It is made up of the same monoclonal antibody found in trastuzumab (Herceptin) attached to a chemotherapy drug known as DM-1. In this type of drug, known as an antibody-drug conjugate, the antibody acts as a homing device, taking the chemo drug directly to the cancer cells.
A study of patients with advanced breast cancer who had previously been treated with trastuzumab and a taxane (either paclitaxel or docetaxel), compared giving ado-trastuzumab emtansine with the combination of capecitabine (Xeloda) and lapatinib (Tykerb). The patients who got ado-trastuzumab emtansine were more likely to have their tumors shrink and lived longer.
This drug is given as an injection into a vein (IV) every 3 weeks. Common side effects include fatigue, nausea, muscle and bone pain, low platelet counts, headache, and constipation. This drug can also cause more serious side effects, such as severe allergic reactions, liver damage, heart damage, and lung problems.
Anti-angiogenesis drugs: In order for cancers to grow, blood vessels must develop to nourish the cancer cells. This process is called angiogenesis. Looking at angiogenesis in breast cancer specimens can help predict prognosis. Some studies have found that breast cancers surrounded by many new, small blood vessels are likely to be more aggressive. More research is needed to confirm this.
Bevacizumab (Avastin) is an anti-angiogenesis drug that once showed promise in treating metastatic breast cancer. Although bevacizumab turned out to not be very helpful in the treatment of breast cancer, the anti-angiogenesis approach might still prove useful in breast cancer treatment. Several other anti-angiogenesis drugs are being tested in clinical trials.
Everolimus (Affinitor®): Everolimus is a targeted therapy drug that was first approved to treat kidney cancer. In studies of women with breast cancer, it seemed to help hormone therapy drugs work better. In one study of post-menopausal women with advanced hormone receptor-positive breast cancer that had been previously treated with anastrozole or letrozole, giving everolimus with exemestane worked better than exemestane alone in stopping tumor growth. This lead to its recent approval for use with exemestane for treating advanced hormone receptor-positive breast cancer in women who have gone through menopause. Studies are needed to see if this drug will also be helpful in treating breast cancer in men.
Bisphosphonates are drugs that are used to help strengthen and reduce the risk of fractures in bones that have been weakened by metastatic breast cancer. Examples include pamidronate (Aredia) and zoledronic acid (Zometa).
Some studies have suggested that zoledronic acid may help other systemic therapies (such as hormone treatment and chemo) work better. In one study, the patients getting zoledronic acid with chemo had their tumors shrink more than those treated with chemo alone. Other studies have looked at the effect of giving zoledronic acid with other adjuvant treatment (like chemo or hormone therapy). So far, the results have been mixed. Some studies have shown that this approach helped lower the risk of the cancer coming back, but others did not. More studies are needed to determine if bisphosphonates should become part of standard therapy for early-stage breast cancer.
Denosumab (Xgeva, Prolia) is another drug that can be used to help strengthen and reduce the risk of fractures in bones that have been weakened by metastatic breast cancer. Studies are being done to see if it can help adjuvant treatments work better.
Everything that is done in the world is done by hope.
Your donation will contribute towards this important research! Two Short Personal Messages of Appreciation from our researcher, Army Col. Dr. Peeples
It was nice speaking to you, and thanks again for your interest in our breast cancer vaccine trials.
All the best,
July 23, 2014
Sorry for the delay. I'd be happy to help out on the Advisory Council.
I'm in the middle of starting 2 new clinical trials, so I'm very busy right now, but would be happy to contribute some items in the future.
George, George E Peoples, MD, FACS, COL (ret), MC, USA
Army Col. (Dr.) George E. Peoples explains how cancer vaccines help to combat breast cancer during an interview at San Antonio Military Medical Center. Peoples, director and principal investigator for the Cancer Vaccine Development Program, has helped to develop a vaccine that’s offering breast cancer survivors hope for a cancer-free future. DOD photo by Linda Hosek
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Hypofractionated radiation: Doctors are comparing giving larger daily doses of radiation over fewer days to the standard radiation schedule. Studies in women have shown that, giving radiation over 3 weeks seems to be about as effective as the standard 5-week course. Other studies have looked at giving even larger daily doses over an even shorter time, such as a week. But again, these studies have included few men, if any, so it isn’t clear how helpful these schedules will be in treating men with breast cancer.