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Jq - your definition is incorrect
Adjuvant Therapy for Breast Cancer
Adjuvant therapy for breast cancer is designed to treat micrometastatic disease, or breast cancer cells that have escaped the breast and regional lymph nodes but have not yet had an established, identifiable metastasis.
Erin V Newton, MD Assistant Professor of Clinical Medicine, Division of Hematology/Oncology, IU Simon Cancer Center, Indiana University School of Medicine; Staff Physician in Palliative Care, VA Medical Center
Vin, you contradict yourself
If the SOC is tamoxifen alone or Herceptin alone, then the trial arms could be tamoxifen alone or Herceptin alone vs IO + tamoxifen or IO + Herceptin.
I never said Tamoxifen or Herceptin alone were the single agent SOC.
If the SOC is tamoxifen alone or Herceptin alone....
If IO is the standard of care, your trial can also have two arms, one is the SOC, IO alone vs the combo of IO + your antigen specific antibody, hormone blocker, or antibody drug conjugate.
Note that I said IF the single agent was the SOC. Please show me where I stated that Tamoxifen alone or Herceptin alone are the SOC.
By the way, Herceptin is approved for treatment of HER2 positive cancer as a single agent. From the web link below.
As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as "AC?TH."
With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as "TCH."
Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin)-based therapy (a type of chemotherapy).
Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer.
Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.
Ex, please re-read my posts
You are agreeing with me.
You argue that one can not run a trial to show that PD-1 + SOC can work.
Of course one can do so. You run PD-1+SOC vs SOC. If it works, you get approved. Just like SUNRISE would have.
As far as Herceptin hitting 20% of breast cancer, so what? It is still a blockbuster. There is a reason why this was the first such combo to get to P2.
Bavi's combo trials are not in progress, yet you claim Bavi is ahead of the field. That is total BS.
Vin, tamoxifen by itself is NOT SOC
True, in trials results matter but you should sure as hell have some idea of mechanism when you design trials, especially in combination trials.
I did notice you failed to acknowledge you were wrong when you said that 20% of HER positive tumors meant that only 20% of breast tumors express HER. As I pointed out, and the MAYO clinic site confirmed, HER positive tumors refers to tumors which HER2 is OVER-expressed based on histochemical assays, or FISH assays. Got it?
What are you talking about? These are the options. If the SOC is tamoxifen alone or Herceptin alone, then the trial arms could be tamoxifen alone or Herceptin alone vs IO + tamoxifen or IO + Herceptin. If the IO is the standard of care, your trial can also have two arms, one is the SOC, IO alone vs the combo of IO + your antigen specific antibody, hormone blocker, or antibody drug conjugate.
Vin, mechanism of action matters not
when you compare trial arms. You're trying to beat SOC. You don't measure MOA as an outcome. You measure OS or PFS in the control arm (e.g. chemo + adjunctive hormonal therapy, which is standard of care) versus the experimental arm (chemo + adjunctive hormonal therapy + downstream 1.0 anti-XYZers).
You can't isolate the effect of adjunctive hormonal therapy because it's in both trial arms.
Got it?
Vin, here's the Mayo Clinic link
Mayo Clinic states Her-2 breast cancer is 20% of all breast cancers
How Many Are HER2-Positive?
The Mayo Clinic estimates that about 20 percent of breast cancers are HER2-positive. Younger women are more likely to be HER2-positive than older women.
HER2-positive breast cancer tends to be more aggressive and to spread more quickly than other cancers. That’s why it’s important to find out if the cancer cells in your body contain this protein.
OK, Vin, it's you against Mayo Clinic
Guess who I'm going with?
The Mayo Clinic estimates that about 20 percent of breast cancers are HER2-positive. Younger women are more likely to be HER2-positive than older women.
You are correct about the monoclonal Ab, but
the therapies mentioned by Vinmantoo, such as Xtandi and Tamoxifen, however, are hormonal treatments (not Mabs) often used in breast and prostate cancer.
As the use of these hormones are Standard of Care for various types of these cancers, how do you expect to prove that these adjunctive hormonal therapies make a difference with I/O 1.0 downstream inhibitors?
How do you separate out the effect of the adjunctive hormonal therapy from the actual chemo/radiation given for the breast or prostate cancer?
The answer is you can't. You would have to run trials with some patients receiving chemo only + anti-XYZ downstreamers and the other arm receiving chemo + anti-XYZ + adjunctive hormonal therapy, to see if the adjunctive hormonal therapy really made a difference.
But that's not the way those trials you cited are designed. And they CAN'T be designed that way, because that would entail a departure from SOC, leaving off the adjunctive hormonal therapy.
You can't do that.
You can't run a trial off SOC to prove adjunctive hormonal therapy synergizes with anti-XYZers. You can't.
OK, Ex, did you actually read the studies you posted
None of them uses adjuvant hormonal therapy in combination with downstream 1.0 inhibitors.
Not one.
Yes, there is one study with HER2+ positive receptor breast cancer, but no mention of Herceptin (which is a limited field anyway as only 20% of breast cancers express this gene receptor.)
Ditto for all the others. No tamoxifen, no Xtandi. No Herceptin.
Mike, being optimistic after extensive research
is different than being blindly optimistic.
Conversely, being miserable for the sake of being miserable, whether or not you've researched the drug, is unfortunately all too common as well.
The stock market provokes a lot of people to vent their spleens; it's just a reality - and while I may not agree with it, I accept it.
Adjunctive chemo or adjunctive hormonal
therapy, either way, you have no evidence for enhancing your solo I/O 1.0 downstream inhibitors with adjunctive approaches. There's just no evidence.
Those studies may be pending, but so are the Bavi studies with NCCN, MSK and AZN. And they're much closer to starting.
We all need to take a step back once a week and consider our options. If we believe enhancement of I/O 1.0 downstream inhibitors with adjunctive agents is the way forward, it would be best to sell PPHM and move on.
Older chemo adjuncts do not equal 2.0
I feel what has been underemphasized is single agents IOs in combination with targeted anti-proliferative antibodies (e.g. Herceptin) or growth factors (e.g. tamoxifen or Xtandi) or with antibodies that specifically bind cancer cell antigens and have been shown to elicit efficacy own their own.
Geo, you are correct; the field is moving that fast
Opdivo has dislodged Yervoy in melanoma, but the concept remains the same - COMBINE upstream and downstream inhibitors for an I/O 2.0 approach.
AZN and the other big players clearly see the future in combination therapy. Durvalumab and Bavi, in my view, will lead this development of I/O 2.0
We have to realize how fast the field is accelerating. We have a lot of posters here still focusing about Bavi's status in the I/O 1.0 solo paradigm, without considering the great combinations coming in I/O 2.0
Regards,
Joe
Vin, immuno-oncology 2.0 is coming
I have never had a problem with anti-XYZ downstream agents. Yes, clearly they do work. But you seem to be still inside the Immuno-oncology 1.0 box, focusing only on solo therapy, as if that were the only approach, and the only stock to buy.
Other investors are watching the major players involved in Immuno-oncology 2.0, and see the focus on combination therapy. Yes, downstream inhibitors work well for a minority of patients. That was the conclusion of I/O 1.0.
If an investor believes I/O research is complete and 1.0 is as far as the field will go, well, then it would be correct to sink all funds into BMS and MRK.
Just please consider that others are following thought leaders in the field, and think I/O 2.0 heralds a different approach.
Regards,
Joe
I suppose data does need to be analyzed
Are you new to biotech?
jq, I do hope you realize we don't have those results yet
EOM
Vin, anti-PD1 Mabs are not the home run you're looking for
Too few responders. Overstimulation of Th1 cell-mediated immunity prompting autoimmune disorders and severe side effects for the minority who do respond.
25% of the initial 40% responders relapse anyway after 3 years.
Wishing that Bavi had a 30% response rate similar to anti-PD1s is missing the point.
The idea is how do you improve that response rate and minimize side effects.
Investors here have an idea.
You are bound to disagree, so I do post this for others.
Regards,
Joe
Prayers for Krak and his family
So sorry for your loss. May God look after him, always.
Joe
Vin, my responses to your responses
Quote:1 - Yes, the stock price is bad; so are the vagaries of biotech.
Many biotech stocks make money for their investors.
Yes, and biotech is as stable as McDonalds and Phillip Morris; everybody makes money; nobody loses money.
Quote:2 - But the science has not changed from day one. Nor from the first day of SUNRISE suspension post first look-in. PS is still a highly immunosuppressive molecule. Bavi and betabodies still cover up PS to turn the immunological lights back on. Nothing has changed on that front. Nothing.
The hoped for mechanism for how Bavi might work hasn't changed, but the Sunrise failure along with ALL the previous clinical trial failures makes it far less likely Bavi will prove an effective anti-cancer agent. What has changed is that several single agent anti-ligand or anti-receptor treatments have been approved and are efficacious. Big money is behind these to expand their usage as single agents, and also in combination. That also doesn't bode well for PPHM and Bavi.
Your anti-ligand and anti-receptor treatments have a 30% response rate at best; the side effects are significant and limit treatment severely for many; not really as promising as you say.
Quote:3 - Chemo is poison. Bavi doesn't work well in a poisonous environment apparently, despite the fantastically weird super efficacious Doxi control arm. So are the vagaries of biotech.
Chemo is still widely used and can be very effective, as cisplatin in testicular cancer shows. There is no evidence or data to back up your statement that the Sunrise control arm was super efficacious. I have stated multiple times that it doesn't make sense to combine cytotoxic agents with immune modulators, but apparently the PPHM "brain" trust are too stupid to recognize the problems. That doesn't bode well for PPHM investors.
Chemo works for essentially two cancers; you are right that testicular cancer is one of them; the other is Non-Hodgkins lymphoma; as for the big ones, unfortunately the treatments are dismal; the mortality for breast cancer s/p chemo hasn't changed much in 50 years; colon, pancreatic, lung, and ovarian have similar terrible track records; try cisplatin and adriamycin and doxorubicin - see if your heart is still beating afterward (awful cardiotoxicity)
Quote:4 - BMS, Merck, Roche, and AZN have invested BILLIONS in the anti-PD1, anti-PDL1 mabs. Only BMS and Merck are raking right now because they were first in line. But the others aren't giving up. Why?
That is completely false. Roche and AZN sure as hell aren;t giving up. If those giants were giving up then PPHM is even worse off than I have stated.
OK, try reading my sentence again. I said they are NOT giving up. You misread the sentence, friend.
Quote:5 - Well, how 'bout combo therapy. It is a phenomenon well-known to the alternative/complementary medical field for decades. In fact, the whole Wall Street biotech immunotherapy racket is a rip-off of what natural holistic doctors have been saying for years.
As John McEnroe used to say, You cannot be serious!
Millions and millions of people have pursued the complementary route to address their cancers; Germany anyone? You are inside a modern box of thinking and I wish you a happy escape.
Quote:6 - You don't treat breast cancer with just DIM (diindolylmethane, an anti-estrogen supplement); you add beta-carotene from natural sources (usually 8-10 blended organic carrot juices per day, plus duneliella algae food carotene - often to the tune of 200,000 IU daily), plus massive doses of Vitamin C, plus a no-sugar diet, plus alpha-lipoic acid, plus selenium, plus extra zinc to improve the zinc/copper ratio, plus Turmeric, plus Holy Basil.....etc.
As John McEnroe used to say, You cannot be serious!
You have much reading to do. Virtually all of the above supplements/vitamins listed above will shift the immune system to the Th1 cell-mediated immunity axis (cancer-fighting); IL-2, Natural Killer, CD8, and macrophages are all potentiated strongly by many natural remedies; have you forgotten that the taxanes were first isolated from the Yew tree?
Quote:Well, Warren Buffet always says, "Buy and hold...forever."
Warren Buffett never said anything even remotely close to that.
See 4ourRetirement's Buffet video link
Regards,
Joe
THE ESSENTIAL SCIENCE HAS NOT CHANGED
A few thoughts:
1 - Yes, the stock price is bad; so are the vagaries of biotech. The delay is painful for all. No doubt.
2 - But the science has not changed from day one. Nor from the first day of SUNRISE suspension post first look-in. PS is still a highly immunosuppressive molecule. Bavi and betabodies still cover up PS to turn the immunological lights back on. Nothing has changed on that front. Nothing.
3 - Chemo is poison. Bavi doesn't work well in a poisonous environment apparently, despite the fantastically weird super efficacious Doxi control arm. So are the vagaries of biotech.
4 - BMS, Merck, Roche, and AZN have invested BILLIONS in the anti-PD1, anti-PDL1 mabs. Only BMS and Merck are raking right now because they were first in line. But the others aren't giving up. Why?
5 - Well, how 'bout combo therapy. It is a phenomenon well-known to the alternative/complementary medical field for decades. In fact, the whole Wall Street biotech immunotherapy racket is a rip-off of what natural holistic doctors have been saying for years.
6 - You don't treat breast cancer with just DIM (diindolylmethane, an anti-estrogen supplement); you add beta-carotene from natural sources (usually 8-10 blended organic carrot juices per day, plus duneliella algae food carotene - often to the tune of 200,000 IU daily), plus massive doses of Vitamin C, plus a no-sugar diet, plus alpha-lipoic acid, plus selenium, plus extra zinc to improve the zinc/copper ratio, plus Turmeric, plus Holy Basil.....etc.
Well, you get the idea. COMBO therapy. Plus, if someone has sizable, advanced breast cancer, it's probably a good idea to cut out as much out as possible. The tumor burden changes bio-electromagnetics throughout the body, thereby stressing it greatly; this is also why Bavi can't kill it.
But chemo and radiation stress the body even more, to the point that most cancer patients in this country die from chemotherapy. The researchers know it. The doctors know it. The nurses know it.
The only one who doesn't know it is the patient. They're just the wallet paying for it all despite ever more deaths from cancer over the past 50 years (cancer is soon to pass heart disease as our nation's #1 killer).
7. So why hold on to your shares. Well, Warren Buffet always says, "Buy and hold...forever." Yeah, I know, it already feels like forever, and that's disappointing for us long-suffering longs, but "c'est la vie."
8. I like the post on Avid being PPHM's lifeboat, otherwise Tustin would be packing boxes. True enough. Well, doesn't the BOD get any credit for thinking Avid through and pursuing it. NO small biotech out there has what PPHM has. Not one. Think about that.
9. I'm still adding when I scrounge up dry powder. That's my choice. You may not agree. Fine. I don't care.
10. My view is that someone will buy the PS platform sooner or later. For the grumpy bears, I know that is little consolation. But in my view, it's only a matter of time. The combos will demonstrate Bavi's critical role, and then it's just formalities from there.
Best regards always,
Joe "Six-Pack" Sulaco
YOU WANTED A MANUFACTURING COMPANY, YOU GOT IT
Avid III coming...and more.
$56 million in net profit soon - whoa.
Just keep expanding, PPHM, and you'll have $100 million in NET PROFIT soon enough.
For a little biotech, outrageous.
Add compelling data for synergistic I/O combinations, and an AZN partnership (isn't this where it's all heading?) will finally make the bulls happy here.
Regards,
Joe
Senrex, Jed Wolcott does not agree with you
He is the lead melanoma researcher in the world at the foremost cancer research center in the world: MSK.
While you are giving up on Bavi, he is not.
When ol' Jed throws in the towel, maybe I'll start to think about wallpaper glue for my PPHM stock certificates for my bathroom.
Hasn't happened yet.
So Sunrise didn't deliver. Gosh, welcome to Biotech.
Only a FEW of the even the biggest BP players have made any real progress in I/O anyway (BMS and Merck). J&J, Pfizer, Gilead, Roche, and Sanofi have NOTHING. Repeat, n o t h i n g.
But you want Tustin's little antibody to sweep 'em all.
Real quick.
Unreasonable. The field is too dynamic. The immune system is one heluva greased pig. Tough to pin down, let alone understand.
But so many seem to have it all figured out. Except the researchers actually doing the work.
I've quadrupled my shares with this recent retail wash out and will continue to average down.
Yeah. Guess I'm a fool.
This is biotech.
Regards,
Joe
He brought Bavi "to" Phase III, not "through" Phase III
Your focus on semantics does not deflect your inability to acknowledge the coming Bavi I/O trials THIS YEAR
Chemo is toxic to patients and doesn't work with Bavi; OK, big deal, MOVE ON, and sell your shares to me for $0.02 pps.
Quite a bargain in your view.
Joe
You guys make it sound like I/O is as sharply defined as a new razor blade
It ain't. Most of big pharma can't figure it out. Bavi has lots of pure I/O combos coming up (forget chemo already), THIS YEAR.
An experiment is not a failure if it tells you how to use your drug correctly.
Please sell tomorrow. My plan is to pick up 100,000 shares for 2,000 dollars. Please don't let me down.
Joe
The time to buy is when THERE'S BLOOD IN THE STREETS
Can't be repeated enough.
The emotional train wrecks on this Board won't listen anyway, though.
I'll buy your shares for $0.02 pps. Dart will get yours for a penny.
BYE BYE RETAIL
Joe
Mortality rates for most solid cancers haven't changed
in 50 years. Chemo has been a disaster. It doesn't mix well with patients and it doesn't mix well with Bavi.
Please sell all tomorrow.
Joe
I look forward to buying your shares tomorrow
for $0.02 pps. A real bargain. You can cash out and buy a burger and fries. I'll enjoy the pure I/O trials free of chemo, with Bavi leading the way. Oh, and by the way, they're happening THIS year.
Joe
Hope it won't be a stretch for you to sell me your shares
tomorrow for $0.02 pps. You're getting a real bargain. You consider your shares "worthless," so I'm offering an infinite markup.
Blood in the streets? TIME TO BUY.
Joe
You speak with emotion
Bavi's place is the I/O, not chemo. Garnick didn't "kill" the drug, he brought to Phase III.
Please sell me your shares tomorrow for $0.02 pps. A bargain for you. For your "worthless" shares.
Joe
REALIST, Bavi's potential is clearly now with I/O
Not chemo. An experiment is not a failure if it tells you how to use your drug correctly.
Roche, GILD, J&J haven't made any headway with I/O - ever wonder why?
You want a smooth road to riches. Ain't happening that way, bud.
This is a true disappointment, no doubt. But Bavi doesn't synergize with chemo. Let's move on to anti-PD1 potentiation
Please sell your shares to me tomorrow. I'll take 'em off your hands for $0.02 per share. A bargain for your "worthless" shares.
Joe
IFU, it's a rapidly evolving field
Roche J&J, GILD, and many other big BPs are behind in development compared to Merck, BMS, and AZN in immunotherapy. You're upset that they're also behind PPHM?
Today's announcement is more about the death of chemo than Bavi. Just wait. When Bavi is bought out because it turns non-responders to anti-PD1 into responders (a pure immunotherapy environment), then the many thousands who will sell all tomorrow will truly realize their foolishness.
Joe
Realist, not true
What we learned today is that Bavi and Chemo-treated patients don't get along.
Bavi and anti-PD1 and anti-PDL1 is a different story. Chemo is going out the window....FAST - Immunotherapy is the new paradigm, where Bavi has its place...
The greatest irony of all will be watching the scolding bears sell their stake tomorrow - only to realize later that Bavi finally found its true place - with I/O agents only
No experiment is a failure - if it tells you how to use your drug correctly
Joe
North, a spread can certainly reduce risk of buying too high while still capturing stock at ultra-low prices
Dart will be there, tripling his holdings.
Panic is what the players want. And panic there will be.
Joe
PPS hits 2 cents tomorrow - I'll be there
Gotta get retail out of this stock - tomorrow is the day
Confident I can get 100,000 shares for $2000 bucks.
Please sell so I can BUY when there is blood in the streets
Eastcoast, OUTSTANDING POINT
We learned something important - Bavi and Chemo hate each other.
Let's get Bavi with other I/O drugs and we'll start seeing great results.
Joe
$2000 dollars may buy 100,000 shares tomorrow
Just be aware of that.
Regards,
Joe
IFU - 10,000 bucks will buy 50,000 shares tomorrow
Easily - RETAIL WANTS OUT, JUST AS PLANNED
North, just set your limit to $0.10 pps
You'll get them!!
Go for it - RETAIL GET OUT
Regards,
Joe
BUY WHEN THERE IS BLOOD IN THE STREETS
Bavi improves anti-PD1 and anti-PDL1 response rates. That, and Avid, are worth more than $2 pps.
Please sell me your shares tomorrow at $0.10
I'm buying when there's BLOOD in the streets.
RETAIL GET OUT
Joe
RETAIL GET OUT - I/O potential is INTACT
Can't wait to pick up 25,000 shares tomorrow for $2500. Really.
Retail will bail in droves and I fully expect a low of $0.10/pps. My buy order at $0.10 pps is in.
None of this weird Doce historical performance touches our Bavi + anti-PD1 synergistic combos and improved percentage of responders.
I think an Astra-Zeneca deal may soon be announced.
BUY WHEN THERE IS BLOOD IN THE STREETS.
Joe