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Brian Nichols, NicholsToday (504 clicks)
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Cancer is the second leading cause of death in the U.S., with nearly 1.6 million new cases each year that account for over 550,000 deaths. The disease costs the U.S. healthcare system an estimated $124 billion annually with breast cancer being the highest cost accounting for $16.5 billion. Breast cancer is also the most common form of cancer among women, with over 230,000 new cases of invasive breast cancer expected to be diagnosed this year that will account for up to 40,000 deaths.

Last week I had the privilege of speaking with one of the true pioneers in breast cancer research, Dr. George Peoples. Dr. Peoples is the Chief Surgical Oncologist and the Director of the Cancer Vaccine Research Laboratory at the CBCP Immunology and Research Center. He is the PI on multiple cancer vaccine clinical trials being conducted at WRAMC, and has written extensively on the immune response to cancer. He is now most famous for developing NeuVax, a potentially breakthrough drug that is being tested in Phase III trials.

The drug reportedly cuts recurrence rates in half and looks to enter the market and treat a particularly underserved area of cancer. Dr. Peoples has talked extensively, throughout the U.S., on breast cancer and is one of the brightest minds in the field. This particular vaccine has been under-development since Dr. Peoples first began working on the drug back in the early 1990s.

After reading countless reviews of the drug, hearing just as many personal testaments of the drug's effectiveness, and seeing a focus story on the lives NeuVax has touched, on News Channel 5 in my hometown of Nasvhille, TN, I decided to reach out to Dr. Peoples to discuss the vaccine, among other topics. The goal of this interview was to eliminate speculation, discuss facts and goals, along with obtaining the real story behind NeuVax and its clinical trials from an actual physician who has many years of experience in conducting clinical studies; a physician who just so happened to develop the drug and is one of the brightest minds in immunotherapy research and breast cancer treatments. It was an absolute honor to have the opportunity to ask questions provided by readers to a true pioneer in cancer research - a decorated physician that is single handedly changing the way we view and treat cancer.

The transcript of the interview has been edited for length, grammar, clarity, readability and syntax.

Brian Nichols

Today, I am speaking with the director and principal investigator for the Cancer Vaccine Development Program at the San Antonio Medical Center, Dr. George Peoples. First off, I would like to say thank you for taking the time to discuss the advancements of cancer treatment along with answering a few questions to educate others about the disease. The first question I would like to ask you is, why is it that until now there been so few advances in the treatment of cancer and what is it that makes cancer such a complicated disease to cure? And also, what triggers a cell to become cancerous?

Dr. Peoples

There have actually been many advances in cancer treatment over the past 20 years particularly against specific types of cancers. Overall, the mortality rates associated with most cancers have decreased. Unfortunately, these have not been as dramatic or as rapid as we would want them to be. Outcomes from cancer are directly related to the stage of the disease when detected which makes early detection essential. But as for a cure, it will likely come through prevention.

One third of cancers could be prevented if people would stop smoking. Other cancers are the result of less apparent causes, but these are likely a combination of factors like a genetic predisposition coupled with an environmental exposure. For these types of cancer, an effective cancer vaccine may be the required element to prevent cancer formation. Ultimately, the diseases that have been cured/eradicated from the planet have come through vaccination like small pox.

Brian Nichols

According to recent studies, nearly 70% of the general public believes that the risk of dying from cancer is increasing. But the truth is actually the opposite. Why does the public share this perception?

Dr. Peoples

People hear about cancer frequently through the media. The perception is that the rates of cancer are increasing. Fear, coupled with a poor understanding of the advances in treatments, lead the general public to conclude falsely that mortality rates are increasing.

Brian Nichols

You are most known for your research of breast cancer and your theories on the immune system's response to cancer. Could you please explain how the immune system can be effective in the treatment of breast cancer or any cancer for that matter?

Dr. Peoples

The immune system is designed to protect us from harmful attacks from foreign invaders like viruses and bacteria, but it is also well equipped to help rid the body of old, dying, or damaged cells. It has been long understood that the immune system can detect cancerous cells because they begin to look more foreign to the immune system or become harmful to the host. Over the past few decades, we have learned a great deal about how the immune system does this. This knowledge has led to ways to exploit components of the immune system, antibodies such as Herceptin, or specific stimulation of the immune system, vaccines such as Dendreon's (DNDN) Provenge, or unleashing the immune system with checkpoint regulators such as Yervoy.

Brian Nichols

NeuVax by Galena Biopharma (GALE) is a drug that you helped to develop and it uses the body's immune system to prevent recurrence. Could you please explain how the drug works, in layman's terms.

Dr. Peoples

Cancers use a variety of ways to promote their own growth, and one mechanism is to upregulate growth factor receptors. One such receptor is HER2. Breast cancers that express high levels of HER2 are particularly aggressive. Fortunately, the monoclonal antibody, Herceptin, is very effective in blocking HER2, and this therapy has been effective in treating the 20% of breast cancers which have the highest levels of HER2 and are likely dependent on this receptor for survival. Unfortunately, another 50-60% of breast cancer patients have tumors that express some level of HER2, but Herceptin has not been proven effective for these patients. Therefore, they are not eligible for Herceptin. The HER2 protein is not expressed at any appreciable level on normal adult tissues, so even low levels of this potentially dangerous protein is detectable by the immune system. This has been known for 20 years.

NeuVax is made up of the most recognizable piece of the HER2 protein to the immune system, the peptide E75. This peptide is mixed with GM-CSF, a FDA-approved immune stimulator, and injected into the skin. The GM-CSF draws immune cells to the injection site where they encounter a very large deposit of the HER2-derived peptide. The immune system picks up the peptide and presents it to the immune system which generates an army of killer T cells with the ability to recognize and kill any cancer cell expressing even the smallest amount of the HER2 protein. As it turns out, the tumor cells with less HER2 are less aggressive, and they are easier for the immune system to kill. While, Herceptin is quite effective in the patients with the highest levels of HER2, we have shown that the vaccine working in combination with the antibody provides a one-two punch that is extremely effective in preliminary studies.

Brian Nichols

Some have argued that because NeuVax was unsuccessful when used on an unhealthy immune system, it could disappoint when used on a healthy immune system. Why is it that NeuVax responds to a healthy immune system but not an unhealthy immune system?

Dr. Peoples

We have never really used NeuVax on patients with unhealthy immune systems. Now, many cancer vaccines trials have failed because they have focused on late stage or metastatic patients. In these patients, the tumor burden, specifically its suppressive effects on the immune system, is likely the cause of the failure of the vaccines to overcome the disease. One potential answer is to test vaccines much earlier in the disease process.

Personally, I favor testing the vaccines in cancer patients after they have completed multi-modality therapy (surgery, chemotherapy, radiation therapy, etc as needed) and are clinically disease-free but who are risk for recurrence. This allows us to use the vaccine while their disease burden is at its lowest in order to tip the balance in favor of the immune system.

Brian Nichols

In the 200 patient trial back in 2001 the drug cut recurrence rates in half, while the control group was consistent with historical averages. In the upcoming 700 patient trial, will the participants be chosen in the same manner as in the earlier 200 patient trial that was so successful?

Dr. Peoples

Overall, the phase 2 trial was successful with a 50% reduction in recurrence but failed by a single recurrence from being statistically significant (p<0.08). In discussions with the FDA after presenting them the phase 2 data, two strategic decisions were made: 1) to concentrate on the HER2 low- and intermediate expressing patients (IHC 1-2+ which makes up about 50-60% of breast cancers) since Herceptin was approved in the adjuvant setting for the HER2 3+ patients during our phase 2, 2) to enroll only node-positive patients (the phase 2 had both node positive and high risk node-negative) because the risk of recurrence is higher in these patients making the number of patients necessary for the phase 3 smaller leading to a more efficient trial.

The overall results of the phase 3 trial may be better in these patients than in the phase 2 since all of the patients in the phase 3 will receive the optimal dose of NeuVax (only a third of the phase 2 patients received the optimal dose) and all will receive boosters (only half of the phase 2 patients received boosters). The best results in the phase 2 trial were in the patients that were optimally dosed and boosted.

Brian Nichols

Let's take a look at other treatments that are working to fight breast cancer. What are your thoughts on Selective Estrogen Receptor Modulator (SERM) drugs such as Eli Lilly's (LLY) Raloxifene and its effectiveness at preventing recurrence? How do these therapies relate to NeuVax in terms of efficiency?

Dr. Peoples

Hormonal therapies to include SERMs and aromatase inhibitors (AIS) are a proven mainstay in breast cancer treatments. All of the patients enrolled to our vaccine trials have remained on their hormonal therapy throughout the studies, suggesting that vaccinations are safe when done concurrently as well as our results are additive to the known benefits of these hormonal agents.

Brian Nichols

Anyone who follows the advancements of the disease is familiar with Roche's (OTCQX:RHHBY) $5 billion drug Herceptin, but what about Tykerb® (lapatinib), a drug by GlaxoSmithKline (GSK) that is sometimes used in place of Herceptin? In fact, some say it's used when Herceptin is no longer working. Would there be any benefit to testing NeuVax with Tykerb?

Dr. Peoples

Tykerb is not currently approved in the adjuvant setting; however, it is likely that NeuVax would be synergistic with Tykerb just as it is with Herceptin. One of the mechanisms behind this synergism is that the amount of HLA molecules (the proteins that present E75 to the T cells) is increased dramatically when HER2 is blocked from signaling. Therefore, either compound could lead to the cancer cell becoming much more recognizable to the immune system and specifically to the NeuVax-induced killer T cells.

Brian Nichols

Did you have high expectations before the pilot trial began?

Dr. Peoples

Several authors have published on the potential of synergy between antibody and vaccine approaches. Furthermore, several mechanisms have been postulated that would lead to this synergy especially with Herceptin and a HER2 directed vaccine. We have previously published our work specifically addressing the benefits of E75 and Herceptin in conjunction. So, based on all of the above, we expected to see a clinical benefit in the pilot patients; however, we never expected the findings to be so dramatic.

Brian Nichols

Now that you have seen the efficiency of the two drugs when used together, what do you hope to accomplish with the Phase II trial?

Dr. Peoples

We need to confirm the findings of the pilot trial in a prospective, randomized, blinded manner.

Brian Nichols

Could NeuVax+Herceptin ever become a drug to itself, where it's manufactured as one drug, depending on the success of the trial?

Dr. Peoples

Unlikely, as the two drugs have different routes of administration.

Brian Nichols

Correct me if I am wrong but the pilot trial with Herceptin+NeuVax showed a 0% recurrence rate among those treated with both drugs and a 12% for those treated with Herceptin alone? This proves the combination to be successful. The reality of the trial is that the conjunction treatment doesn't have to maintain a 0% recurrence rate. If Herceptin results in recurrence of 12-15% and the conjunction treatment is 10% then it shows a significant advantage over Herceptin alone. This gives NeuVax two avenues to succeed. If the Herceptin+NeuVax trial is as successful as the previous trial, in what situation would you treat a patient with both drugs compared to just one or the other? What benefits are there to using both drugs?

Dr. Peoples

The first point is correct. We expect the phase 2 combination trial to show a benefit over Herceptin alone, but we do not anticipate, nor have we planned for, the combination arm to continue with 0 recurrences.

If the PRESENT trial is successful, then NeuVax monotherapy will be pursued in the HER2 low- and intermediate-expressors, and the combination of NeuVax and Herceptin will be pursued in the HER2 high-expressors. This strategy will allow all HER2 expressing breast cancer patients (80%) to have access to NeuVax.

Brian Nichols

I have just a couple more questions that I would like to ask you if it's okay? A couple months ago a relative of mine was diagnosed with breast cancer. Her treatment includes chemotherapy and radiation after surgery revealed that the cancer had spread to the lymph node that connects to the breast tissue. She is reluctant to explore other areas of treatment through clinical studies. One reason being her physician's lack of support or comfort with the idea. Do you have any theories of why people are so hesitant to embrace new treatments of cancer and do you think physicians are being properly educated on the advancements in oncology?

Dr. Peoples

Fortunately, I believe with the advances in the information age and social media, both physicians as well as patients are being educated on the benefits of research trials. Huge efforts have been made to make information about clinical trials available. For example, anyone can go to clinicaltrials.gov and search for the clinical trials that may be appropriate and available for them. The site has separate portals and information for physicians and patients.

Brian Nichols

Last question, do you think there will ever come a time when chemo and radiation will become outdated or considered a secondary treatment?

Dr. Peoples

The trend has clearly been toward more specific and less toxic therapies; however, chemo and radiation have proven success that will have to be equaled before they will be made obsolete.

Companies and/or drugs discussed in this interview: Dendreon's Provenge, Bristol-Myers' (BMY) Yervoy, Eli Lilly's Raloxifene, GlaxoSmithKiline's Tykerb, and Galena BioPharma's NeuVax.

Source: NeuVax Developer Dr. Peoples Eliminates Speculation For Facts