KZA Media Thread, page-1222

Yes thanks onesurfed.....I am receiving alot of reporting from that breast cancer conference, last week.  It comes free via email from a subscription to a group called PracticeUpdate. Maybe you have the same subscription.

Anyway the information that is of most interest to me, is clinical trials using PI3k drugs that are already approved / or new PI3k inhibitors. Still nothing though of another PI3k drug other than Paxalisib in the brain. Dozens of PI3K trials in all different types of cancers are presently taking place.

Remember the link from Jean Zhao at Dana Farber - dated 18 Nov....where Jean makes reference to an all purpose PI3K blocker...here:

-----
"The reason, scientists at Dana-Farber discovered in a new study, is that BKM120 is not the all-purpose PI3K blocker it was thought to be: instead of thwarting two subtypes of PI3K equally, it shackles one but barely restrains the other. The effect is to deprive glioblastoma cells of one aspect of their cancerous nature while giving almost free reign to another."
-------
Jean designed the current GDC 0084 Dana Farber BCBM trial (you know, that elusive non release of data trial)........

So who is Jean Zhao ? publicity shy that is for sure.

However this fact....last year the FDA hosted a brain mets conference in March -  and asked Priscilla Brastanious and a Mike Davies from M D Anderson to host it (with one other I think) If the FDA ask you to host their 3 day conference - you are somebody, we already know that. At the time and since than Pricilla often thanks Mike for his 2016 landmark PI3k brain studies , which helped lead to her GDC 0084 ALLIANCE trial. But who does Mike accredit/acknowledge ongoing and core studies in PI3k inhibitors - none other than Jean Zhao.

Paxalisib/GDC 0084 is the all purpose PI3K blocker that works in the brain and in all 4 isoforms.

--------
The fact of the matter is the NCI is paying for this ALLIANCE Trial - and Paxalisib is the chosen PI3K inhibitor in this extremely though environment of the brain - where cancers are heavily mutated in the CNS, compared to primary cancers. Brain mets...as we know emanate from lung, breast, skin and blood. No Keytruda, in the ALLIANCE trial, but  Paxalisib. (It crosses the BBB)

PI3K pathways are the most frequently common mutated pathways in cancers.....Paxalisib is the chosen drug ahead of  $120b blockbuster drugs. It makes perfect sense....as suggested by PB to shut down the PI3K pathway first and foremost. Does Keytruda do that - NO.

_____________________

OK if you have not had enough - this from a couple of weeks ago......PI3K drug now in combination with CDK4 inhibition.

In the Priscilla Brastanios ALLIANCE trial - 43% of Brain Mets had actionable PI3K mutations and 50% CDK4 mutations - now we see both of these pathway drugs being trialed working together. That means there is potential for PI3K drugs (us paxalisib) to work in conjunction with Abemaciclib (PB chosen CDK drug)  for basically all or 93% of brain mets.

And this company is capped at US$120m....it is an absolute disgrace and management must soon assume some blame.

Mike Davies, Priscilla Brastanious, Jean Zhao .....consider what they are reporting in studies and decisions made with the use of this drug Paxalisib.

It is not what I say - but a simple conclusion based on facts.

This drug is worth US 1 .5 billion now - based on straight forward logic of its future earnings potential and current risks......that LOOK for yourself, at the companies presentations using peer comparisons. The company must do more in disclosures to convey what you are having to read on an anonymous chatline. Wake up mangement.

-------------------------------------------------
Overcoming Mechanisms of Resistance to CDK4/6, PI3K Inhibition in Breast Cancer

December 4, 2020
Hayley Virgil



Cynthia X. Ma, MD, PhD, discusses several research efforts examining mechanisms of resistance to CDK4/6 and PI3K inhibitors in breast cancer and some of the novel combinations that may possess the potential to overcome this challenge.

What we're trying to do to overcome CDK4/6 inhibitor resistance or to delay this resistance is to add on agents that would inhibit, for example, the PI3K pathway. We have a National Cancer Institute study that is looking at a triplet regimen comprised of the PI3K inhibitor copanlisib [Aliqopa] plus fulvestrant [Faslodex] and abemaciclib [Verzenio]. The goal is that by adding the PI3K inhibitor, we will be able to delay progression on the combination.

The interesting concept here is that copanlisib is intravenously administered and is given once a week on day 1, day 8, and day 15 every 24 days. This drug differs from other PI3K inhibitors that are oral medications that need to be taken every day. The intravenous administration allows [us to deliver] a higher dosage and thus, more complete inhibition of the pathway. The hope is that the triplet will behave like cytotoxic drugs at that time point so that we can prevent the development of resistance.

These triplets [have been found to be] very potent in the preclinical studies and in patient-derived xenograft models. These [regimens are] still [being examined] in the metastatic setting. Whether future studies will bring some of these ideas to the early-stage setting would be interesting to see, although we would have to worry about toxicity.

As you mentioned, these agents are not without toxicity. Were any management strategies in place to combat the adverse effects associated with the triplet regimen in that study?


We did not specify any prophylactic measures, but because copanlisib can cause hyperglycemia, the protocol called for fasting or having a low hyperglycemic diet. Patients could not receive the infusion right after a meal. We also monitor glucose after the infusion for 2 hours. In addition, if the patient experiences diarrhea—both drugs could have overlapping toxicity in that sense—we do advise that physicians prescribe prophylactic antidiarrheal agents. We try to give a very good education to the physicians and coordinators who are participating on this trial so that we can manage toxicities better.