don't remember if I posted this during ASCO--good results for her2 vaccine

Lani · 07-15-2012, 12:26 AM

Breast Cancer Vaccine Reduces Recurrence

Women with a history of HER2-positive breast cancer show lower rates of relapse after inoculation.

A novel hybrid vaccine reduced recurrence rates in patients with HER2-positive breast cancer by 43% after 22 months in early results of a phase IIb randomized clinical trial. Of 201 patients rendered disease free by standard treatment, those who received the vaccination had a recurrence rate of about 10.3% compared to 18% in the control group.

“We need to continue to follow these patients, but there is enough of a trend that a phase III trial is warranted,” says Elizabeth Mittendorf, MD, a surgical oncologist at MD Anderson Cancer Center in Houston and the trial's national principal investigator. The results will be presented June 4 at the 2012 Annual Meeting of the American Society of Clinical Oncology.

Antigen Express of Worcester, MA, the company producing the vaccine and a partial funder of the trial, plans to follow up with a phase III study.

The vaccine teaches CD4+ T-helper cells, immune cells that are critical in mounting a response against foreign invaders, to recognize the HER2 protein, which is expressed at some level in 75% to 80% of breast cancer tumors. The vaccine's hybrid design combines a fragment of HER2 with a novel peptide based on the immune-regulatory li protein that, in laboratory tests, was found to enhance the potency of the vaccine 250-fold.

Because the vaccine is effective in tumors with any level of HER2 expression, it may aid patients who are not eligible for targeted therapy with Herceptin (trastuzumab; Genentech) because their tumor HER2 levels are too low.

If it is eventually approved, the vaccine could be delivered in any physician's office. The ongoing trial included monthly injections for 6 months followed by boosters every 6 months for 3 years. To heighten immune response, the vaccine was paired with an immune stimulant known as granulocyte macrophage colony-stimulating factor, which was also given to patients in the control arm of the trial.

The trial targets women who are disease free after standard-of-care treatment rather than those with metastatic disease, because the vaccine was not likely to overcome aggressive and invasive tumors. “It's a paradigm shift in trial design for cancer vaccines,” says Mittendorf, who is now developing a trial giving the vaccine with chemotherapy prior to surgery to test whether inoculation during immune system reconstitution improves outcomes.

©2012 American Association for Cancer Research.

karen z · 07-15-2012, 11:35 AM

Fantastic news.
I wonder how long before a reality for most?

Posts · 07-15-2012, 12:13 PM

Help me suss out the targeted patient, please.

Those who are HER2+ and NED after treatment that included Herceptin or a targeted therapy?

And/or those who are NED after treatment without targeted therapy because their HER2 tumor levels were too low.

Thanks Lani!

'lizbeth · 07-15-2012, 08:44 PM

This is my trial. I'm in the GP2 vaccine arm because I'm HLA-A2+. SandraGa is in the arm with the AE37 vaccine by Antigen Express.

Here is the link for the clinical trial:

http://www.cancer.gov/clinicaltrials...archid=9088859

The Phase III should be starting soon. Five years of data needs to be collected. However the phase III could take longer, possibly 10 years, because it takes up to 5 years for full enrollment. This is why I encourage everyone I can to participate. The faster we enroll, the sooner that everyone will have an opportunity to have the vaccines.

You need to enroll by six months after finishing Herceptin or treatment for the above trial.

I have discussed other vaccine clinical trials with my nurses. There is one that is combined simultaneously with chemo and Herceptin. Another vaccine trial is for lower expressors of Her2 who are not eligible for Herceptin.

I don't know of anything similar that is a treatment to actually prevent recurrence.

I can say that I felt much better after receiving the injections, not immediately afterwards as I had flu-like symptoms, and some serious headaches. But over time it seemed like my health felt like it was improving. I suspect that I benefited from the treatment, but of course, it is a blind study and I won't know until the 5 year mark if I received the vaccine or the GMCSF only.

I encourage others to please consider joining this clinical trial, or any trial that is suitable to you. The faster the trials reach full enrollment the sooner treatments will be available to all of us.

anna4969 · 07-18-2012, 08:43 PM

One more vote for vaccines!! I was also in a similar trial whereby I had the gp2 vaccine 30 minutes after my Herceptin infusion. Dr. Mittendorf is my doctor. She is brilliant and is working diligently to make these vaccines our bullets for recurrence.

I fully agree with Lizbeth, I have felt better after the vaccine both physically and mentally. It gives one the opportunity to help other breast cancer patients and yourself. I wouldn't hesitate to participate in anyone of these vaccines. The side effects are minimal and quickly fleeting, so very easy to do. (Thank you Sandra for encouraging me to participate

)

Be well

'lizbeth · 07-19-2012, 07:30 AM

Oh Anna 4969, finally someone else in my GP2 arm! I'm so glad. When I first signed up only a few women were trying the vaccines - and none in the Walter Reed that I could find. I was happy to have the company when Sandra enrolled.

I feel much better. The side effects were pretty severe on me at first, but I suspect I really, really needed the vaccine. I had terrible headaches and a big local response. I learned to have my Tylenol handy.

It is exciting to see preliminary data coming in that shows a difference between the vaccine and the GMCSF only.

Best of all - we get to be part of finding a treatment that actually PREVENTS cancer! Yeah!

anna4969 · 07-19-2012, 10:58 AM

Yeah for the GP2, the E-75 and AE37!!!

Funny how everyone's body is so different in reacting. I had minimal side effects that maybe lasted 6 hours, if that. And I absolutely got the GP2 with GM-CSF because I was in a phase 1 trial checking for safety.

Be well everyone

'lizbeth · 07-20-2012, 09:10 AM

Anna4969,

I am so happy you did the phase 1.

I too got at least 2 small injections of the GP2 vaccine in the phase 2, the rest of the injections were randomized and I won't find out for another 2 1/2 years.

chemteach · 07-26-2012, 05:46 AM

I will be seeing my oncologist next week, and I will ask him about this. I am completely unfamiliar with trials, but am nearing the end of my year of Herceptin. After reading the article, I might be a candidate. I hesitate because of the questions I have....how do I pay for this, what do all those acronyms stand for, will I miss a lot of work again this year, what about side effects, and so on. I notice there are several sites in TX, but do I need to be military to go to Ft. Hood? What a wealth of information you all are! Thank you.

'lizbeth · 07-26-2012, 05:56 PM

Chemteach,

Elizabethtx is in the trial in San Antonio as well - and her site is not military.

HLA-A are a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus on human chromosome 6p. The HLA genes constitute a large subset of the Major histocompatibility complex (MHC) of humans, according to Wikipedia. It is another way of subdividing cancers, such as Her+ or ER-.

E75 is another name for Neuvax to prevent Her2+ breast cancer with HLA-A2 positive. NeuVax, developed by Galena Biopharma, Inc., is a peptide-based vaccine aimed at preventing or delaying the recurrence of breast cancer in cancer survivors who achieve remission after standard of care treatment (e.g., surgery, radiation, chemotherapy).[1] It consists of the E75 synthetic peptide initially isolated from HER2/neu proto-oncogene combined with the immune adjuvant, granulocyte macrophage colony stimulating factor (rhGM-CSF from yeast).[2] NeuVax works by harnessing the patient’s own immune system to seek out and attack any residual cancer cells that express HER2/neu.

NeuVax has been tested as adjuvant treatment in nearly 200 breast cancer patients over a total of 5 years, and has shown to be safe and effective in Phase 2 trials.[4] As a result, two additional NeuVax trials underway are: (1) a 700 patient Phase 3 trial for FDA approval[5] and (2) a 300 patient Phase 2 trial studying the combination of NeuVax and Herceptin®. (Again Wiki)

On Yahoo Finance I found this info:

E75 is over 1/2 year ahead of AE, but appears to be harsher on patients in the initial clinical trials.
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The first of these vaccines to be explored in the adjuvant setting was E75 (OT 6/25/08). In the largest of the E75 trials, which Dr. Peoples reported on at the meeting, approximately 180 node-positive and high-risk, node-negative women maximally treated and disease-free entered the Phase II study. A total of 101 HLA-typed A2-positive patients were vaccinated and 79 A2-negative patients were followed prospectively as controls.

One of the drawbacks of using a peptide-based vaccine, Dr. Peoples explained, is that it is HLA-restricted and therefore only useful in HLA-A2 positive patients. That strategy, however, was chosen specifically because HLA-A2 positive patients make up about half of the HER-2/neu breast cancer population.

Locally, 82% of patients experienced Grade 1 toxicities and 18% had Grade 2 toxicities, while systemic toxicity was mild, at 15.5% for Grade 0; 69%, Grade 1; 13%, Grade 2; and 2%, Grade 3.

Local reactions can be fairly intense, Dr. Peoples noted. We split our injection into two sites. You will see a lot of erythema and some induration. These are the type of reactions you can get and they only make up a minority.

Two other peptides, GP2 and AE37, were also studied in Phase I trials modeled after the early studies of E75 and showed similar safety profiles.

GP2 is close in relationship to E75, being a short peptide that stimulates CD8 killer cells and a CPI epitope. However the peptide is found in another portion of the protein and there are different characteristics associated with GP2 in terms of its binding, potentially for the subsets of T cells it stimulates. AE37, on the other hand, is a longer peptide and stimulates CD4 helper cells.

Similarly, local toxicities for AE37 were 40% for Grade 1 and 60% for Grade 2. Systemic toxicities were 13%, Grade 0; 73%, Grade 1; and 13%, Grade 2

This information is a little old, more recent interim reports have been published on the trials.

chemteach · 07-27-2012, 06:48 AM

Very helpful!! I will talk to the oncologist and find out more about this. I certainly am interested in participating.

Rolepaul · 07-27-2012, 07:36 AM

Time to win with this. Nina is now considered disease free and is being seen in the same office! May all of you fighting the disease have the chance to find the succes we did with Nina's CNS (brain and spine) treatments. I think that it is likely that there will be a more focused treatment for various organ involvement, but this vaccine could be very important for the treatment of HER+ women, even before there is disease discovered!

We walked through Yellowstone and Grand Teton last week for Nina's birthday. Our anniversary and my birthday happened within the previous two weeks. Nina was given less than a 5% chance of seeing these events last Christmas when there was brain and spine involvement. We followed through with a proven treament that has now made her disease free (she was NED in all areas other than the brain), although there were blood cells and markers that indicated disease prior to her treatment starting. She now has normal level markers, no signs of disease radiology, no sign in blood cells, etc. Here is hoping the vaccine makes that permanent.

Lani, thank you as always.

Ellie F · 07-27-2012, 08:40 AM

Rolepaul
Did Nina receive this particular vaccine or am I misunderstanding?
Really pleased to hear that nina had such a good response to treatment.
Ellie

Rolepaul · 07-27-2012, 09:22 AM

Since Nina has not been considered NED until this coming week, she was not eligible for the vaccine. I am not one to take "No" easily so I will get her enrolled and let the forum know what needs to happen. I have access at a fairly high level with MD Anderson through means I prefer not to say. I was aware of the study, but was also aware of the requirements for inclusion.

As I say, I am just an engineer at a fairly low level in the pharmaceutical industry that has been involved with some good projects. This carries a fair amount of ability to push for a treatment plan and a fair amount of knowledge about how the drugs work. It can be a help and also let you know the chances of various outcomes. When you hear that there is 50% mortality within 6 weeks and 95% mortality within 12 weeks with the involvement seen, that can either scare you or motivate you. The later happened for Nina's case.

Nina's treatment results are going to be in a medical journal article within the next few months. Due to patient confidentiality, you will not know it is her. Based on the indication, treatment, and outcome it will be evident. I hope that one day, the method is routine. Right now it is not. I want that to change.

Rolepaul · 07-27-2012, 09:28 AM

There might be a problem with the AE work as I think there is an issue with the current presidnet of MD Anderson having an interest in the AE organization. I hope that does not affect the ongoing work. I know the AE vaccine tends to be well tolerated and is relatively inexpensive to produce. Maybe I should not know about the cost. OOPS.