Your neoadjuvant speculation is the sharpest line in this post — the hazard ratio being “exactly what you would get if you give pembro before surgery instead of after” reframes the vaccine not as a breakthrough but as possibly redundant immune priming. But here's a variable I'd want in the data trickle that even the journals may never deliver: how many randomized patients ever received the full bespoke course? A personalized neoantigen vaccine has to be manufactured per patient — sequencing, synthesis, QC — and patients can progress, withdraw, or run out of time between biopsy and dosing. Manufacturing failures and dropouts before the first dose all sit inside the intention-to-treat effect being reported.
You wrote that you still don't know “how many patients were censored, lost to follow-up, did not complete therapy etc.” — I'd add: did they not complete because of toxicity, or because the product was never made in time? If it's the latter, the leak tells us nothing about whether the biology works.
As he is known to do, Dr.Prasad, bursts bubbles with his probe, tumbles hubris with his intellect and keeps the rebellion against high-handed humbug, nourished, vital and growing, with his raw courage.
He has the essential gift of being hilariously funny, to keep us with his outstanding humanity.
Dr. Prasad is right to insist that a promising clinical result is not a license for sweeping claims. The Phase 3 trial provides strong evidence that adding an individualized mRNA vaccine to post-operative pembrolizumab improves recurrence-free and distant-metastasis-free survival in patients with resected high-risk melanoma. The similarity in hazard ratios to those reported for pembrolizumab before surgery followed by additional pembrolizumab after surgery is striking, but it may be coincidental. Still, it makes one pause to ask: Why do we need the vaccine if we can get equivalent results without it? Identical hazard ratios from different trials do not establish equivalent treatments, much less prove that the vaccine contributed nothing. The comparison raises a question; it does not answer it. The trial does not establish longer overall survival, efficacy in other cancers or metastatic disease, or a general lesson about mRNA vaccines. Dr. Prasad is also right that topline announcements and staged disclosures make independent appraisal difficult.
Dr. Prasad is less persuasive when he moves from justified skepticism to conclusions that are not well supported. Calling the vaccine “incredibly costly” requires evidence about actual manufacturing costs and eventual pricing. We can make assumptions, but we don’t really know. Declaring the technology financially lucrative likewise goes beyond what we know. Commercial potential and demonstrated profitability are two different things. It is tempting to argue that the success of an industry-funded trial obviates the need for further federal support for cancer research, but one successful trial cannot establish that conclusion. Industry and federal funding need not serve the same purposes. Dr. Prasad’s claims may prove right, but so far, I’m not convinced. The irony is that his strongest point supplies the standard by which his own conclusions should be judged: do not extrapolate beyond the evidence. The result of this trial is neither proof that the mRNA cancer-vaccine revolution has arrived nor evidence that the vaccine is merely pre-surgery Keytruda in disguise. The trial appears to represent a meaningful advance in one defined setting, with important questions still unanswered. Skepticism should keep the claims within those boundaries, not move the goalposts in the opposite direction.
Saw this in MSM, made a note to self: Gonna wait and see what Vinay says about this. I'm not an expert, so I don't understand the medical stuff, but I get the point. Thank you!
Your neoadjuvant speculation is the sharpest line in this post — the hazard ratio being “exactly what you would get if you give pembro before surgery instead of after” reframes the vaccine not as a breakthrough but as possibly redundant immune priming. But here's a variable I'd want in the data trickle that even the journals may never deliver: how many randomized patients ever received the full bespoke course? A personalized neoantigen vaccine has to be manufactured per patient — sequencing, synthesis, QC — and patients can progress, withdraw, or run out of time between biopsy and dosing. Manufacturing failures and dropouts before the first dose all sit inside the intention-to-treat effect being reported.
You wrote that you still don't know “how many patients were censored, lost to follow-up, did not complete therapy etc.” — I'd add: did they not complete because of toxicity, or because the product was never made in time? If it's the latter, the leak tells us nothing about whether the biology works.
As he is known to do, Dr.Prasad, bursts bubbles with his probe, tumbles hubris with his intellect and keeps the rebellion against high-handed humbug, nourished, vital and growing, with his raw courage.
He has the essential gift of being hilariously funny, to keep us with his outstanding humanity.
Dr. Prasad is right to insist that a promising clinical result is not a license for sweeping claims. The Phase 3 trial provides strong evidence that adding an individualized mRNA vaccine to post-operative pembrolizumab improves recurrence-free and distant-metastasis-free survival in patients with resected high-risk melanoma. The similarity in hazard ratios to those reported for pembrolizumab before surgery followed by additional pembrolizumab after surgery is striking, but it may be coincidental. Still, it makes one pause to ask: Why do we need the vaccine if we can get equivalent results without it? Identical hazard ratios from different trials do not establish equivalent treatments, much less prove that the vaccine contributed nothing. The comparison raises a question; it does not answer it. The trial does not establish longer overall survival, efficacy in other cancers or metastatic disease, or a general lesson about mRNA vaccines. Dr. Prasad is also right that topline announcements and staged disclosures make independent appraisal difficult.
Dr. Prasad is less persuasive when he moves from justified skepticism to conclusions that are not well supported. Calling the vaccine “incredibly costly” requires evidence about actual manufacturing costs and eventual pricing. We can make assumptions, but we don’t really know. Declaring the technology financially lucrative likewise goes beyond what we know. Commercial potential and demonstrated profitability are two different things. It is tempting to argue that the success of an industry-funded trial obviates the need for further federal support for cancer research, but one successful trial cannot establish that conclusion. Industry and federal funding need not serve the same purposes. Dr. Prasad’s claims may prove right, but so far, I’m not convinced. The irony is that his strongest point supplies the standard by which his own conclusions should be judged: do not extrapolate beyond the evidence. The result of this trial is neither proof that the mRNA cancer-vaccine revolution has arrived nor evidence that the vaccine is merely pre-surgery Keytruda in disguise. The trial appears to represent a meaningful advance in one defined setting, with important questions still unanswered. Skepticism should keep the claims within those boundaries, not move the goalposts in the opposite direction.
Amen, and extremely well said as usual, VP! Thanks again for your honest and straightforward assessments of the healthcare “news”.
Saw this in MSM, made a note to self: Gonna wait and see what Vinay says about this. I'm not an expert, so I don't understand the medical stuff, but I get the point. Thank you!
🙄