Immunotherapy is detrimental when added to H&N XRT

[seper]

Lee et al, Lancet 2021.

What if opposite is also true, i.e. "inverse abscopal effect"?

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[evilbooyaa]

I mean I hesitate to say statistically detrimental, but certainly no benefit. The same concerns people have about TILs and immune suppression around the tumor and inability to do that when radiating large ENI fields is the question here.

I do wonder if the initial data in non-metastatic disease is mostly going to all be consolidative a la PACIFIC. PACIFIC 2 will be positive unless protocol was amended to mandate durva consolidation in the placebo arm, but I wonder if the concurrent IT is the way to go forward in cancers treated with definitive radiation.

 

[ramsesthenice]

The same concerns people have about TILs and immune suppression around the tumor and inability to do that when radiating large ENI fields is the question here.

Maybe. This was a SOC plus trial. If you blast away the TILs with big fields you could expect that you would potentially compromise the efficacy of the IO and see equivalence between SOC and SOC + IO. In a purist sense that is what you see here. But if the trends held up and SOC + IO really were inferior to SOC that would suggest something more were going on. Exhaustion? Anergy? Toxicity? Lots of possible options.

 

[TheWallnerus]

"Survival curves separated in favor of placebo. 'It was really surprising and a little bit [alarming].'" - Nancy Lee

 

[Lamount]

It seems hard to imagine that concurrent IO adds anything to 6-7 weeks of fractionated RT. Any activated T-cells that localize to the tumor end up getting fried.

I don't know if this is being looked at in H&N, but I think it would be more interesting to investigate a sequential model like PACIFIC: CRT -> [IO vs. obs]. Create a bunch of tumor antigens with CRT... THEN give the IO.

 

[ramsesthenice]

It seems hard to imagine that concurrent IO adds anything to 6-7 weeks of fractionated RT. Any activated T-cells that localize to the tumor end up getting fried.

I don't know if this is being looked at in H&N, but I think it would be more interesting to investigate a sequential model like PACIFIC: CRT -> [IO vs. obs]. Create a bunch of tumor antigens with CRT... THEN give the IO.

There is a lot we don't know. I intuitively agree with you but keep in mind that IO also works on migrating APCs including DCs which migrate to the lymphatics fairly rapidly. In something like H&C where you extensively treat the lymphatics they may not fare any better but in principle treating concurrent with fractionated RT could still work. And with SBRT type dosing there is some data that concurrent is better than sequential (though this is not a universal finding). The data from the DUART (durvalumab with RT for bladder) looked pretty good but it was a single arm trial. That said, the pembro iteration of NRG-GI002 was stone cold negative. We should get interim data for the alliance adjuvant IO anal trial this year and I have heard they are looking good.

Is anyone confused yet? I vomited trial results on the page with little context for a reason. The whole thing is a dumpster fire at this point. So many trials. So little coordination or central messaging.

 

[TheWallnerus]

The whole thing is a dumpster fire at this point.

Hear hear!

 

[mheat3]

Is anyone confused yet? I vomited trial results on the page with little context for a reason. The whole thing is a dumpster fire at this point. So many trials. So little coordination or central messaging.

This should be the last sentence of every conclusions/discussion section of these trials. Perfectly summarized.

 

[Mandelin Rain]

This should be the last sentence of every conclusions/discussion section of these trials. Perfectly summarized.

The drug companies are scrambling for indications for THEIR drugs. They know the first to publish will become the standard. Easier to beat placebo than to beat the established standard (biosimilar) IO drug in a trial.

Thus, we're seeing all kinds of **** hitting walls in hopes some sticks.

Patients and rationale be damned. We answer to the shareholders.

 

[thecarbonionangle]

This should be the last sentence of every conclusions/discussion section of these trials. Perfectly summarized.

is the GOG designing H&N trials now? many are saying it

 

[deleted941485]

The drug companies are scrambling for indications for THEIR drugs. They know the first to publish will become the standard. Easier to beat placebo than to beat the established standard (biosimilar) IO drug in a trial.

Thus, we're seeing all kinds of **** hitting walls in hopes some sticks.

Patients and rationale be damned. We answer to the shareholders.

Im sure the medoncs will conclude RT is detrimental to this whole process. ALL HAIL IPI/NIVO!!

 

[ramsesthenice]

Im sure the medoncs will conclude RT is detrimental to this whole process. ALL HAIL IPI/NIVO!!

As far as IO goes the net effect on RT utilization will be interesting to see. A lot of us are seeing a pretty good increase in referrals for SBRT for oligo progressors and many med oncs are full in on this. Before anyone celebrates too much, they are doing a zillion trials trying to show that IO works as an adjuvant for pretty much all diseases instead of RT or chemo. Any that show equivalence will almost certainly become THE SOC in very short order. They are also trying to use them for brain Mets etc. Time will tell if that happens but swapping out 25 fraction adjuvant therapy with 3-5 fraction SBRT is not a winning formula in the long run.

 

[deleted941485]

As far as IO goes the net effect on RT utilization will be interesting to see. A lot of us are seeing a pretty good increase in referrals for SBRT for oligo progressors and many med oncs are full in on this. Before anyone celebrates too much, they are doing a zillion trials trying to show that IO works as an adjuvant for pretty much all diseases instead of RT or chemo. Any that show equivalence will almost certainly become THE SOC in very short order. They are also trying to use them for brain Mets etc. Time will tell if that happens but swapping out 25 fraction adjuvant therapy with 3-5 fraction SBRT is not a winning formula in the long run.

Yeah that only works if they are repeat patients not replacing upfront CRT with some garbage oligo progression months afterwards just so I can give them SBRT and collect the professional equivalent of a Denny's Grandslam to one or two metastatic lesions.

 

[ramsesthenice]

Yeah that only works if they are repeat patients not replacing upfront CRT with some garbage oligo progression months afterwards just so I can give them SBRT and collect the professional equivalent of a Denny's Grandslam to one or two metastatic lesions.

hey, you laugh, but as COVID dies down and marijuana is legalized in more states there are going to some super rich Denny’s franchisees. That and IHOP.

 

[deleted941485]

hey, you laugh, but as COVID dies down and marijuana is legalized in more states there are going to some super rich Denny’s franchisees. That and IHOP.

Lol well like most rad oncs I don't own the pancake house (Facility) to make that worthwhile.

I smile a bit when I see someone taking a drag on their fancy vape machine or just a plain old cigarette. It gives me hope. lol