TRIPLE POSITIVE GROUP
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Here is an article that is a little old, but it explains the differences between the types of vaccines. Interestingly enough, this was on a pharmacy financial page.
Monday, May 30, 2011
Filling an Unmet Need: A Comparative Look at Generex and RXI Pharma's Breast Cancer Vaccines
On June 5th, RXI (RXII) Pharmaceuticals will be presenting 36 month data for their E75 HER2/neu peptide vaccine, also known as NeuVax. The updated Phase II study results in adjuvant breast cancer will be announced during a panel RXI is hosting timed in conjunction with the 2011 ASCO Annual Meeting. RXI stated that the 24 month landmark analysis was first presented at the ASCO Breast Cancer Meeting in October 2010.
Subset Analysis of Nonrandomized Trials
The 24 month landmark analysis presented at ASCO's Breast Cancer Meeting was actually a cumulative finding of nonrandomized Phase I/II studies of E75, based upon a subset analysis of subjects. While the studies have enrolled 188 subjects, due to trial design, 72 patients received less than what was determined to be the optimal biologic dose. The 24 month landmark analysis revealed a recurrence rate of 6.5% in the E75 group vs. 14.5% in the control group (p=0.08).
A subset analysis of the study results, as researchers cull the data, found a grouping of patients with low HER2/neu expression, IHC 1+ and 2+, that are node positive, and whom received six month cycles of booster shots that benefited most from E75. The booster program was initiated after the ongoing studies revealed waning immunity of the E75 vaccine. The researchers found that amongst this subgroup of patients, the E75 vaccine reduced disease recurrence rate by ~ 50% compared to unvaccinated women.
Limitations of E75 in Filling an Unmet Need
Herceptin, the blockbuster cancer fighting drug from Roche (RHHBY.PK) and Genentech, is currently approved by the FDA for women with metastatic HER2-positive disease, and women with earlier stages of HER2-positive disease as adjuvant treatment (treatment after initial treatment, such as surgery) either alone or as part of a regimen with chemotherapy. The IHC test gives a score of 0 to 3+ that indicates the amount of HER2 receptor protein in tumors. Women with IHC positive scores tend to respond favorably to Herceptin. Samples with strong HER2 overexpression, IHC 3+, indicate eligibility for Herceptin therapy. This population makes up approximately 25% of HER2/neu breast cancer patients.
A new presentation available at RXI's website states that E75 will fill an unmet need, treating low HER2/neu expressing patients, who test in the IHC 1+ and 2+ range. As noted above, this is in contrast to Herceptin, which is available to patients that are >IHC 3+. The RXI presentation cites Herceptin's 2010 worlwide revenue of over $5 billion, while RXI's latest press release states that over 200,000 women in the U.S. are diagnosed with breast cancer annually, 75% of whom test IHC 1+, 2+ or 3+, with 25% those with HER2 3+ disease eligible for Herceptin, with E75 targeting the remaining 50% of HER2 1+ and 2+ positive patients. I will explain why I feel that may be a target that E75 can not hit, while explaining how another peptide based vaccine, from Generex (GNBT) Biotechnology's wholly owned subsidiary Antigen Express, can only make that claim.
Peptide Based Vaccines and Alleles
E75 is HLA-A2/A3+ restricted, since the peptide binds to this specific HLA allele. This means that patients that are HER2 1+ or 2+, and HLA-A2/A3-, may not benefit from this vaccine. HLA-A2/A3+ positive patients make up a good portion of the HER-2/neu breast cancer population, yet leaves near 30% out of the picture.
The United States Military Cancer Institute has conducted the various clinical trials of E75, as well as for two other peptide based vaccines, AE37 and GP2. AE37 is Generex's Ii-Key hybrid HER2/neu peptide vaccine. At ASCO 2009, the USMCI outlined the percentages of patients that have these various alleles. They found that out of 363 enrolled patients, 172, or 47.4%, were HLA-A2+, while 191, or 52.6%, were HLA-A2-. Additionally, of 100 patients typed for HLA class II, 31 were HLA-DR3+."
Similarly, in December 2010, at the San Antonio Breast Cancer Symposium, the USMCI noted the amount of HER2/neu patients that were HLA-DR3+ in their various peptide based vaccine studies, which was double the expected 13%. Patients that are HLA-DR3+ with low HER2 expression would also not be suitable for E75 or GP2. The researchers found that of the three peptide vaccines they are investigating, they believe Generex's AE37 may overcome weakly binding MHC II phenotypes, and may be used to treat low HER2 expressing subjects with the DR3+ allele.
Comparing the Unique Differences of E75, AE37, and GP2
Earlier this year, the USMCI researchers published a report titled Comparison of Different HER2/neu Vaccines in Adjuvant Breast Cancer Trials, which appeared in the February issue of Expert Review of Vaccines. The report compared the clinical characteristics of three different immunotherapeutic peptide vaccines designed for immunotherapy of breast cancer. The order of potency of specific HER2 immunity induced by the vaccines was: (1) AE37, followed by (2) GP2, followed by (3) E75.
The researchers explain that the three peptides studied in their trials are similar, but have unique differences. AE37 is the most individual, as it is a HLA class II-binding peptide, stimulating CD4 T-helper cells, and generating longer term specific immune responses as compared to the others. GP2 and E75 are HLA class I restricted, stimulating CD8+ T cells, while AE37 is a promiscuous peptide, which they explain as allowing AE37 broader relevancy.
AE37 Available to Both Node Positive and High Risk Node Negative Patients
The FDA awarded E75 a Special Protocol Assessment for a Phase III clinical trial in the adjuvant setting for node positive women with low-to-intermediate HER2+ status. This will be the first randomized study of E75. AE37 is currently in a randomized, multi-center Phase II trial in patients who have completed standard therapy for node-positive or high-risk node-negative breast cancer expressing at least low levels of the HER-2/neu oncogene. The ultimate goal of the AE37 study is to demonstrate that, after a follow-up period of 24 months, the relapse rate in the AE37 group of the study is less than half the relapse rate in the control group. The reported interim results of this study show that AE37 is on track to achieve that positive endpoint.
AE37 Alone Wholly Fills the Unmet Need
The results being presented on June 5th for E75 stem from a subset analysis of a nonrandomized Phase II study. The expected positive results should surely help RXI's rebounding stock. I don't think RXI would host this pending panel and announce 36 month results unless they like what they see. However, when compared to AE37, E75 comes with certain specific allele restrictions, limiting the patient population this vaccine can treat, beyond the reports from USMCI researchers that AE37 appears more potent and longer lasting.
When considering the claim that a peptide based vaccine targets the remaining 50% of HER2 positive patients (HER2 1+ and 2+) who achieve remission with current standard of care, but have no available HER2 targeted adjuvant treatment options to maintain their disease free status, I find that it is a claim that can only wholly be made for Generex's AE37.0 -
U ladies amaze me all the time, u are all so intelligent and use u'r intelligence so wisely----Now this is what I read--I'll shorten it for u
Blah, bla,blah,blah, blah blah,--that's sad cuz that's kind of what I understood and I used to be able to read and absorb immediately. OHHHH
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Thank you ladies for all of the congrats! It's not over yet though. Fighting off the worst case of constipation ever and taking steroids and anti nausea meds to try to keep from vomiting this time. One more week...and some se should subside...not all.. But at least the nausea. The steroids are making me quite loopy. Makes me nervous:(
On a great note though...I had my echo dine today and my ef was exactly the same as when I started. Around a 67. So far so good...fingers crossed.
Fluff thanks for all of the info. I am a bit nervous about the financial side of the trial, but, I will cross that bridge later.0 -
Well done Jennifer. I remember counting the days post each treatment until I felt better. I was lucky in that I didnt have any sickness but I still suffered constipation and Dand generally felt yuk. Knowing that this would pass got me through.
Solt: hope you get some answers. I had palps during Herceptin (and a history of them prior to BC) Had more echos than was standard and loads of ECG. Finally had the 24 hour holter and nothing showed, no arrythmia and the echos showed that the heart was structurally sound. All very frustrating. I have come to accept that periodically I will have spells of palps and there are certain triggers. Even during an episode, my pulse is always normal. Taking it kinda reassures me, although the palps are unpleasant.
Kayb: interesting article about Al. My 84 year old aunt is suffering with pain and I'm sure its the Al. Can you post the source of the article please.
Hi to everyone from a stormy, grey England...............
Liz
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OK Jenn, u'll be out of this soon, just know that.
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I had my daughter (the mother of 6 boys) give me a #2 buzz a week before my surgery.
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Hooray for all the great news!!!!
Jennifer, you're there! Im three weeks pfc and i couldnt wait to get here. Finally, food tasted better just yesterday! Hang in there.
Going for the 12th of my 12 weekly herceptin tomorrow, so it's a milestone for me, too.
Hugs to the new ladies ❤.0 -
bcbarbie, Wow, you got herceptin every week ? I wonder why so many of us get it every 3 weeks? Actually I wish I could get it every week,going for a year is so long...
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Eileenohio - I think the original protocol was weekly infusions for a year. Then they did a study comparing weekly infusions to every 3 week infusions and found that they were comparable. Both methods give you the same total dose over a year, so the every 3 week infusion is a higher dose than the weekly infusion dose.
see slide 13 which shows graphs comparing the two schedules.
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Omaz, thanks. I thought Barbie said she is getting 12 weekly then she is done.
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eileen - some docs prescribe weekly Herceptin during chemo, then after chemo is complete they move to the every 3 weeks dosing. I think that is what bcbarbie meant - she just finished chemo.
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Thanks Kathy..., Oh now I understand. That makes sense.
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Jennifer I found metamucil 3X a day as directed was the best help for constipation for me along with my probiotic NutraFlora from the vitamin shoppe)
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Lago I had the exact opposite and it's violent and I still have it-every single test and they have no idea why--we're all so different and I took immodium for a whike but it wasn't stron enough so now I'm on reg. meds it helps a bit. But constipation is so painful alot of the times.
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When will I poop??? HELP! tee hee.
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Oh Pbrain Im sorry, they'll be someone along to give u advice I never had that problem--I always had the opposite and still do. LOL
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Uuuggghhhh...too late for me. Headed into the cancer center for fluids and other fun stuff to help with constipation. I am so so so sick. I tried to stay on top of everything but it did not work:(
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When I had big C I just went to XLax chocolate when all the natural, easy-going stuff failed.
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Hi Ladies,
My mind is semi out of this first chemo cloud. I've been Skimming posts, still in a little fog.Thank you for all and I am trying all suggested. After severe bone pain Sunday, then Monday night, and up till this morning with severe headache. Getting better now. My DM has been caring for me, pushing fluids, food. Now with a little more nausea and constipation. Sorry to be graphic. Started as D and now C since Sunday was last. Doing muralax, but nothing. Will try benefiber and lastly exlax. I have been pushing fluids. Maybe I need more fluids. Also havent been eating as much as normal. i dont know. Going to go rest.0 -
My worst constipation was the first round. Once I figured what worked for me the next 5 rounds were much easier.
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Well, I'm an 8 Metamucil pills a day gal, and I wasn't able to take them the night before surgery. Plus I got some info in the mail from the hospital saying stop any herbal, non-herbal supplements 1 week before surgery. So I stopped for two nights. Now, not much happening in the peristalstis category ;-)
I will definitely post for advice on constipation though when I start chemo. In the meantime, everyone talks here about steroids. When do they come into play in treatment?
I love you guys! I know I sound like the dude in Wayne's World, but I do!
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pbrain - some oncs just do steroids in the pre-meds on the day of chemo. Others have you take a dose the day before, day of, and for a couple of days afterward. It is supposed to help with nausea and swelling - general inflammation.
Also, my BIL the gastroenterologist recommends Miralax. I know some of the ladies here have used it and it has worked but for others it has not been enough. I think he likes it because it is pretty gentle.
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Oh I'm so sorry u girls are suffering so---It's got to get better.
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Ha ha, it is no big deal Camil, but thanks to everyone for the chemo constipation advice. I've always been so good in that area, quite the champion of dumping. So this is just strange for me. Hoping tomorrow I get the gold medal. And I'll look into both Colace and Miralax.
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Miralax is an osmotic laxative, while Colace is a stool softener - colace does not have a laxative feature. Both of these should be used short term only as they can be "habit forming" for the body.
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Eileen, SpecialK is right, i had the weekly herceptin with the chemo. Twelve in all. Today was the 12th!!!! Now i get a three-week rest then i will be getting it every 3 weeks but at 4mg/kg. i think the weekly was 1/3 that dose.
Pbrain, Smooth Move tea never failed me. I take it on the night of chemo. Even with herceptin alone.0 -
I know this is so oldfashioned but it usually worked good old prunes or prune juice warm--Or prune juice and apricot nectar mixed warm. This was a big things years ago and usually worked, I know ir silly, but it's natural. Just sayin.
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Just went to the TCH forum and made a discovery that I have to share. At my 16th herceptin infusion the nurse said that since I had no prior issues with herceptin only infusions she would give it to me over 1/2 hour instead of an hour. Well ...I was knocked for a loop. I was so tired that I didn't even know I was probably too tired to drive the one hour home! Took me a week to bounce back. I was also psychologically depressed as well for days after. I've been wondering if that infusion was the cause . Ladies in the forum said it was because the infusion was too fast.
My advice is not to rush your infusions.0 -
This constipation issue was in fact my worst physical chemo SE. Until it happened 2 days after my first chemo, I had no idea how miserable it can be. It is still amazing how in 2 days...the contents of your bowel can just dry up....
I used to be a person who tried to go without meds so it took me two rounds to get it controlled. Stool softeners worked for me but I started them BEFORE treatment.0 -
For the record, the big C with chemo is by far THE MOST humbling experience ive ever had.
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