Vaccine Therapy in Treating Patients With Breast Cancer

[alicem]

I read an article about a breast cancer vaccine study. It said . . . "Breast cancer fueled by the HER2 protein puts women at risk for return of the disease. But there may be a new weapon in the fight. Researchers are testing a military-developed vaccine that should help the immune system fight back. In the study, some patients will get a drug that boosts white blood cell production only. Doctors says earlier studies among military patients found the vaccine shows promise."

Here is the link to the trial study:

http://www.clinicaltrials.gov/ct2/sh...0524277&rank=1

[Pam P]

This is exciting news! I hope there's more info and a chance to be in trials soon. I wonder if it will apply to stage 4 folks?

[alicem]

I just went back and read the criteria, and unfortunately you have to be disease free and within 1-6 months of just finishing treatment. I'm sorry Pam. Here is the inclusion and exclusion criteria . . .



Inclusion criteria:

• Meets one of the following criteria:
  • Lymph node-positive breast cancer
  • High-risk lymph node-negative breast cancer, defined by any one of the following criteria:
    • T2 disease
    • Grade 3 disease
    • Lymphovascular invasion
    • Estrogen receptor- or progesterone receptor-negative disease
    • N0 (I+) disease
  HER2/neu-expressing tumor (immunohistochemistry [IHC] 1-3+ and/or positive fluorescence in situ hybridization [FISH] > 1.2)
• Clinically cancer-free (no evidence of disease) after completion (between 1-6 months ago) of primary standard of care breast cancer therapies (i.e., surgery, chemotherapy, immunotherapy, and radiation therapy as appropriate per standard of care for patients' specific cancer)

Exclusion criteria:

• HER2/neu-negative breast cancers (IHC 0)
• Clinical and/or radiographic evidence of residual or persistent breast cancer

PATIENT CHARACTERISTICS:


Inclusion criteria:

• Female or male
• Menopausal status not specified
• Immunologically intact by recall anergy testing
• Negative pregnancy test

Exclusion criteria:

• Anergic by the Mantoux panel of recall antigens
• Karnofsky 0-60% or ECOG ≥ 2
• Total bilirubin > 1.8 g/dL
• Creatinine > 2.0 g/dL
• Hemoglobin < 10.0 g/dL
• Platelet count < 50,000/mm³
• WBC< 2,000/mm³
• Active pulmonary disease requiring medication that includes multiple inhalers
• Pregnancy
• Breastfeeding
• History of autoimmune disease

PRIOR CONCURRENT
Inclusion criteria:

• See Disease Characteristics

Exclusion criteria:

• <LI style="MARGIN-TOP: 0.7ex">Concurrent immunosuppressive therapy including chemotherapy, steroids, or methotrexate
• Concurrent participation in another experimental treatment (except with permission of the other study investigator)

[Becky]

This is the E75 trial. There (IMHO) are criteria problems with this trial. They test you and your immune system and only accept people who they believe will respond. All others are in the control group.

Secondly, I am afraid of vaccine trials that target Her2. (More on this later). I wish they would target something that cancer cells possess but normal cells do not. Remember that the heart is loaded with Her2 which is why the heart is affected (for some) by Herceptin. You can stop taking Herceptin if need be but a vaccine can't be stopped once injected. Your own body can "kill" your heart and other organs with naturally high Her2. Just my humble opinion. Really look and investigate the criteria of this trial It is extremely lopesided on how they pick their participants (besides the target factor)

[alicem]

Thanks Becky, I am new to looking at clinical trials and I really appreciate you pointing out all the problems. I did not know that the heart was loaded with Her2 cells. I've learned something new.

[StephN]

FYI - there is a new trial on the boards at the University of Washington Tumor Vaccine Group. Just talked to the study nurse there last week. They will be targeting a gene bit that is found in several cancers. They are in the process of writing it so it will be a while, but the ARE looking at other targets for the vaccines.

[Lori R]

Alice,
Thank you for posting and starting the discussion on the E75 trial. I had this on my "fall back" list.

As usual our Her2 sisters are so knowledgeable....I think I'll move this option a little lower on the list. Doesn't sound like I'd qualify and I too learned something about Her2 being in the heart. Becky....thank you for that insight.

Steph..thanks for the update on the Washington group. I wish that I had known about their work earlier in my journey. But... sounds like they are performing some promising research. No pressure but....hurry up...

Lori

[Ellie F]

Hi Lori and all
I too have been looking at vaccine and imunotherapy trials. I have just yesterday got a new onc who has had a 3 year sabbatical at a prestigious uk cancer research centre. He supported what Becky was saying about her 2 heart effects.This lead on to a discussion I posted a couple of weeks ago to try to find out if any sisters had signed up for the CEA or oncofetal protein trials that were news items on the board. These two proteins I believe target other factors that are common on a range of tumours, in fact the CEA protein trial is being used for pancreatic cancer in England at present but not bc.
Ellie

[StephN]

Ellie -
Can you tell us what CEA stands for?

I have a CEA drawn as a tumor marker (CarcinoEmbryonic Antigen), and it is indicative of activity in various cancers. Mine is always below detection level, except when it went up with my brain mets.

[Ellie F]

Hi Steph
CEA is the protein measured for your tumour markers.This trial is NCT00673829 at Roger Williams Medical Centre, Rhode Island. It is funded by an IMPACT grant.The estimate is that between 30-50% of metastatic breast cancer tumours express this protein.My understanding is that if your serum cea>=10ng/ml you automatically qualify for the trial. If your serum cea<10ng/ml tumour tissue must be tested to see if you will qualify.
The second trial is the phase1/2 Quantum imm trial highlighted on clinical trials on the board.This is targeted against oncofetal antigens which apparently have a high percentage on bc tumours.
My onc feels that these are very early developments which will look at safety levels and tolerability. But they have at least 5 years to run so progress will no doubt gallop on.
Hope this is some help
Ellie

['lizbeth]

I saw the Mayo clinic in Scottsdale is also having a vaccine trial. How does that compare to the other trials?

http://clinicaltrials.gov/ct2/show/N...accine&rank=23

[Cynthia]

Friends,

It has been a long time since I last posted. I do, however, continue to follow the discussions and offer my thoughts and prayers to all in our community.

As a graduate of the E75 trial (and its booster program), I would like to weigh in on this discussion. While I certainly am not endorsing any trial or encouraging anyone to participate in anything, I want to make sure that trials are being fairly considered. I would hate to see a potentially promising trial rejected out-of-hand before it is thoroughly and accurately vetted (recognizing of course the inherent uncertainty of any trial.)

First, the trial referenced by alicem in her initial post is the current phase II trial of two newer HER2-derived peptides (GP2 and AE37). I believe that Becky is referring to the E75 peptide trial, and not the GP2 or AE37 peptides. (More about the E75 trial later.)

Second, I understand that the criteria for inclusion in the E75 trial, and other than HLA specificity, disease-free status, and immunologically competent (reactive skin testing), was as inclusive as could be. I disagree with the notion that patients were being cherry picked for inclusion.

Third, regarding the statements about HER2 expression in the heart, please see below….

Breast Cancer Res Treat. 2003 Nov;82(1):23-8.

Analysis of HER2 and HER4 in human myocardium to clarify the cardiotoxicity of trastuzumab (Herceptin).
Fuchs IB, Landt S, Bueler H, Kuehl U, Coupland S, Kleine-Tebbe A, Lichtenegger W, Schaller G.
Department of Gynecology, Frauenklinik, Charité Campus Virchow Clinic, Berlin, Germany. ilka.fuchs@charite.de

PURPOSE: When combined with anthracyclines, the humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) provides significant clinical benefit for women with HER2-overexpressing metastatic breast cancer. However, its use is limited by severe cardiotoxicity. To clarify whether myocardial HER2 and HER4 expression in response to anthracycline exposure and cardiac damage contributes to cardiotoxicity, we assessed expression of HER2 and HER4 in pathologically altered myocardium. EXPERIMENTAL DESIGN: Cardiac biopsies from 60 patients with severe heart disease and cardiac tissue from 35 patients with breast cancer were obtained. Twenty-five of the patients with breast cancer had previously received anthracyclines. Three of 10 anthracycline-naïve patients with breast cancer had received trastuzumab. Expression of HER2 and HER4 was analyzed immunohistochemically (HER2: HercepTest/A0485 (Dako), Cy3 detection (Dianova); HER4: Ab-4 (NeoMarkers)). FISH analysis (Ventana) was used to assess HER2 gene amplification. RESULTS: Immunohistochemistry revealed weak HER2 membrane staining in six cardiac biopsies, appearing as dotted staining of the whole cell membrane and intensified HER2 signal using fluorescent Cy3 labeling. No HER2 membrane staining was detected in the remaining 54 cardiac biopsies or in the myocardium of the 35 patients with breast cancer. HER2 gene amplification was not observed. All specimens showed the mild cytoplasmatic HER4 staining of normal myocardium. No strong HER4 expression was detected. CONCLUSIONS: Cardiac alterations are not associated with an strong increase in HER2 and HER4 levels. IHC detects potential low-level HER2 expression in some samples. However, a more sensitive technique may be needed for studies of the role of HER2 in cardiac tissue. These data do not exclude a role for inhibition of cardiac HER2 expression by trastuzumab in the onset of heart failure in trastuzumab-treated patients.

In this study, minimal amounts of HER2 was detected in 6 out 95 cardiac biopsies (60 with severe heart disease and 35 breast cancer patients). No one is completely sure why Herceptin is cardiotoxic but it’s not because of HER2 expression in the heart. In fact, it is very difficult to find detectable levels of HER2 in any human adult tissue except for cancers. That’s why most vaccines target it. Thus far, no cardiac toxicity has been seen any of the HER2 vaccine trials (Disis).

Finally, the FDA has completed its review of the E75 phase II data and the proposed phase III trial design and has approved the manufacturer's (Apthera’s) SPA (special protocol assessment). Please see the following:

Apthera Secures SPA for Pivotal
NeuVax Trial in Breast Cancer
By Jennifer Boggs

Assistant Managing Editor

After quietly chugging along amid a swirl of cancer vaccine
news, privately held Apthera Inc. popped up on the radar,
armed with a special protocol assessment for a pivotal
Phase III trial of its peptide-based immunotherapeutic,
NeuVax, in early stage breast cancer patients.
The news came only days after fellow cancer vaccine
firm Oncothyreon Inc., of Seattle, reported that Stimuvax
partner Merck KGaA decided to add a Phase III breast cancer
study to its ongoing Phase III study in non-small-celllung
cancer, signaling a re-energized interest in the space
that had been rife with disappointment prior to Dendreon
Corp.’s Phase III success with Provenge (sipuleucel-T) in
prostate cancer.

Apthera’s SPA, finalized after a 21-month process with
the FDA, calls for a single, Phase III trial enrolling 700
women diagnosed with HER2/neu-expressing tumors who
have completed standard-of-care treatment – surgery,
chemotherapy and radiotherapy. Patients also must have a
common HLA haplotype, specifically HLA-A2 or -A3.
The primary endpoint will be disease-free survival,
with the first analysis of data expected to occur after 70
recurrence events, or about three years after the start of
the trial.

The Scottsdale, Ariz.-based firm did not provide a start
date for the study. Nor did it disclose whether it intends to
fund the trial itself or seek a partner to help offset the costs.
Apthera executives could not be reached for further comment,
though Alton C. Morgan, president and CEO, said in a
statement that the SPA “created a value inflection milestone
for both the product and the company.”

Apthera has kept much of its financing private to date,
though earlier this month it licensed commercial rights to
NeuVax in South Korea to Kwang Dong Pharmaceutical Co.
Ltd. in exchange for milestone payments, royalties on product
sales, an undisclosed equity investment and a pledge
from Kwang Dong to invest in a future round of financing.
Founded in 2005 with technology licensed from the
University of Texas M.D. Anderson Cancer Center in Houston,
and the Henry M. Jackson Foundation for the
Advancement of Military Medicine Inc. in Rockville, Md.,
Apthera’s focus centers on a pipeline of peptide-based
immunotherapies.

As the most advanced of those, NeuVax is designed
with the E75 peptide, a rare T-cell peptide believed to boost
pre-existing anticancer immunity, and initially is aimed at
the subset of HER2-positive breast cancer patients who do
not qualify for treatment with Herceptin (trastuzumab,
Genentech).

Earlier in the pipeline, Apthera is working on NeuVax in
prostate cancer. The firm recently reported promising data
from HER2-positive patients at high risk for recurrence at
the American Society of Clinical Oncology meeting in
Chicago, showing that the median time to disease recurrence
from prostatectomy was 14 months for the NeuVax
group vs. 8.5 months for the control group. Data also
showed that patients with stable prostate-specific antigen
throughout treatment exhibited a median time to recurrence
of 42.7 months. ■

Just my two cents.

Stay well.

['lizbeth]

I want to thank both Becky and Cynthia for posting about the E75 vaccine. I'm considering participating in the trial and I'd like to hear both the pro's and con's of the vaccine.

If anyone else has an opinion, comment, experience on E75 please add your 2 cents.

Thanks.