Slightly better answer after the 15 minutes
We will have to wait for the data to KNOW.
My opinion is that it likely benefits all patients or most to some degree, but some are clearly benefitted much more than others. If you could live to 23 months instead of 16, as a median, even if you knew you were not among the patients most benefitted, given our history of approving drugs that only provided 1 month's benefit in some cases, that would be huge. But of course, the 23 months includes the placebo patients and patients initially treated might in fact live longer than 23 months as a median..
As for the combination trial, cancers and the body react to changes. You should really watch some of the science presentations to get a better feel for the dynamism of cancer and the pathology of the disease.
In some cases, just as an illustration, the cancer is invisible to the immune system. Keytruda, which has been predicted to likely make $19 B per year previously, is a drug that turns off a mechanism that prevents certain autoimmune reactions, but it was thought it would therefore allow the body to “see” and identify cancers and destroy them. And it works for some patients and some cancers, and they have approval to use when certain biomarkers are present.
However, when you unmask cancer, the body does not necessarily “see” it and determine it is something that needs to be destroyed. The body may see it as “self” still.
When patients were given some vaccines, think of it like when marines light up a target with a laser so that a smart bomb, dropped by planes, can hit the target precisely. That is a great technology. The body has identified the tumor as something that needs to be destroyed.
However, some of those vaccines only identified 1 or a few targets and when the cancer cells with those targets were eliminated, other cells still existed and those cells became the face of the new cancer that appears to recur, but it is just likely that all the cells were not destroyed with that less comprehensive vaccine, for instance, or a chemo treatment that kills cells but leave cancer stem cells, for instance. Additionally, probably the body turned on defense mechanisms to turn off what it thought was an autoimmune reaction even with those vaccines.
DCVax is a more advanced vaccine and it identifies many or all the antigen targets that the removed tumor tissue contains, at least what the surgeons could remove, and they use the patient's own dendritic cells to identify the tumor's antigens in an artificial environment created for that purpose, In some cancers that is likely all or most of the targets in their body. And then like I said, the immune cells can then identify and destroy those cells, but the body is dynamic. And DCVax' trial actually has better results with tumors that have MORE mutations than fewer mutations because that seems to really allow the body to get all the tumor cells.
In many patients where there was perhaps none or a limited immune reaction to a tumor (without DCVax), and then, when you turn the mechanism on with DCVax, the mechanism that Keytruda turns off, PD-L1 / PD-1, the “mask”, that was not there (because the tumor just did not generate an immune response by itself), now gets turned on by the body to protect itself because the cancer cells are, in fact "you", at least large parts of them. The cancer, by itself, may not have generated an immune reaction at all, prior to DCVax, and therefore it would not have turned on the masking, but now you've generated an immune reaction and the body responds by trying with other mechanisms, to turn it off. So the body thinks the intentionally induced immune reaction is an autoimmune reaction, a bad thing, and it tries to shut it down, and apparently is quite effective at that often, but not always. And as we get better at this all, we'll start to understand all the mechanism that affect that process and make the process of killing the cancer more effective.
So now you’ve identified the cancer to the body with a vaccine, let's say DCVax, but the cells send out some other distress signal perhaps one we know or don’t know, or don't fully understand yet, and now, having “lit up” the tumor, the body tries to stop what it thinks may be an autoimmune reaction by now masking the cancer. So where’s before, when the tumor was removed, there was no masking, after DCVax is administered, in some cases the tumor hides using these other mechanisms. You have to understand the various mechanisms.
So what would you do in that case? Well, we have drugs for that, a few of them, that act in different ways, Keytruda is one of them, Opdivo is another, and there are other drugs that help maintain the immune reaction or, in fact, they turn the masking off that was triggered by the new immune reaction.
So you see, you can potentially see a sign of efficacy in the generation of the masking biomarkers that were not there before, but as with many diseases, there are multiple aspects to consider.
COVID, we have a need to treat the disease, but also the body’s overreaction which can even continue when the body has already mostly eliminated the virus. That autoimmune reaction in COVID is actually what kills most patients, not the pathogen itself.
So doctors need multiple tools and we may ultimately need to assess how we think about treating tumors, as we start to understand the deeper underlying mechanisms and biomarkers and multiple drugs may provide us with a roadmap.
That is a gross oversimplification by a person who is by no means a scientist or doctor. But people can add further clarifications and address ambiguities, as there are many people here with a variety of specialties and specific knowledge.
I hope that helps to explain, in a very simplified and by no means complete way, why you’d look at combinations and a variety of measures to ultimately find a cure for cancer.
In this context, it is very possible that vaccines, and other treatments previously found to be futile, with the right measures and combinations, might ultimately be revived and found to be efficacious. I think Dr. Linda Liau will actually be helping much of the industry to achieve their goals and advance many new drugs in the future, that will in combination make cancer a much more easily managed disease.
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