OUTBACK trial results

[Gfunk6]

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Presented virtually at ASCO: Disappointing But Important: Cervical Cancer OUTBACK Trial’s Negative Results

Women with locally advanced cervical cancer treated with chemoradiation vs chemoradiation --> adjuvant chemo

Equivalent survival but worse toxicity with more chemo.

 

[TheWallnerus]

The more-is-better philosophy in oncology sure seems to get the s**t kicked out of it these days oftener than I recollect.

 

[seper]

I've enrolled a few women on RTOG part of this trial, and pretty much expected negative results. Perhaps a checkpoint inhibitor will pan out eventually

 

[Lamount]

I was just thinking… does anyone know of any phase III trial supporting CT+CRT over CRT (either adjuvant or neoadjuvant) in ANY disease site? I can’t come up with anything off hand.

 

[Krukenberg]

I was just thinking… does anyone know of any phase III trial supporting CT+CRT over CRT (either adjuvant or neoadjuvant) in ANY disease site? I can’t come up with anything off hand.

Nasopharynx. Neoadjuvant gem/cis or TPF has become standard

 

[radiation]

I was just thinking… does anyone know of any phase III trial supporting CT+CRT over CRT (either adjuvant or neoadjuvant) in ANY disease site? I can’t come up with anything off hand.

PACIFIC if you count IO

 

[Lamount]

PACIFIC if you count IO

I feel like giving so systemic chemo sequenced with RT beats people up a lot of the time … and and they don’t end up doing well for one reason or another (evidently not the case in NPX). Perhaps it’s because of immunosuppression that a lot of patients struggle. I think IO is a different entity in this regard

 

[ramsesthenice]

I was just thinking… does anyone know of any phase III trial supporting CT+CRT over CRT (either adjuvant or neoadjuvant) in ANY disease site? I can’t come up with anything off hand.

LARC. It’s more of a combination of trials than a specific phase 3 study. But trimodality is SOC for most of these folks (except for w/w patients or those with lower stage tumors and pCR to CRT following surgery).

 

[fiji128]

I thought this trial was going to be positive for the same reasons why this approach works in LARC. But I guess that's why they run the trails and is why I am always wary when people start spouting about data from such in such series or whatever phase II trail at tumor boards to justify things.

 

[ramsesthenice]

I thought this trial was going to be positive for the same reasons why this approach works in LARC. But I guess that's why they run the trails and is why I am always wary when people start spouting about data from such in such series or whatever phase II trail at tumor boards to justify things.

The problem is that across the board chemo improves OS about 5% in patients with advanced but non-metastatic solid tumors. Its just not that much to begin with. My bias is that its a biology issue. It should go without saying that chemo will help the most in patients with chemosensitive disease and I wonder if "radiosensitizing" doses of chemo have more of a systemic effect on those patients than we appreciate. If so, that could close the gap enough that it is next to impossible to detect a difference between CRT and CRT + Chemo.

PORTEC-3 is an example of a trial that could have helped in this realm but the control arm was RT alone. They called the experimental arm chemoRT but it was really CRT + Chemo. Is it better than concurrent CRT only? Don't really know.

LARC is also a special case. I think RAPIDO is encouraging, but its one study and I am not quite sold that TNT really improves long-term survival and cure compared to the old German regimen with post-surgical chemo. With organ preservation we will never know because TNT already became a new standard since clinical and pathologic responses are, unlike most other disease, in and of themselves important endpoints. In some ways that makes it a much lower bar for success. Clinically meaningful to be sure.

 

[thecarbonionangle]

Maybe gyn oncs should learn to give more chemos rather than just carbo taxol. Or maybe let med onc take over and advance systemic therapy for GYN cancers, which is behind imo.

 

[FrostyHammer]

LARC is also a special case. I think RAPIDO is encouraging, but its one study and I am not quite sold that TNT really improves long-term survival and cure compared to the old German regimen with post-surgical chemo. With organ preservation we will never know because TNT already became a new standard since clinical and pathologic responses are, unlike most other disease, in and of themselves important endpoints. In some ways that makes it a much lower bar for success. Clinically meaningful to be sure

Why shouldn't TNT be delivered though? Do you think the data for adjuvant chemo was particularly robust?

 

[ramsesthenice]

Why shouldn't TNT be delivered though? Do you think the data for adjuvant chemo was particularly robust?

I think something got misconstrued. I love TNT and I do it all the time. All I meant above was that I don't think we are ever really going to know if TNT actually improves OS or MFS because frankly I don't see accruing to a non-TNT arm as part of an RCT anymore. We already know there is meaningful value in TNT if for nothing else of improved response rates and the associate surgical implications. Regardless of long-term oncologic outcomes. They are at least as good if not better.

 

[Palex80]

I think these trial results are important.
Some of you may recall this South American randomized trial that looked at Cis/Gem consolidation post CRT for cervical cancer.
This actually became a trend for a short time and one of the patients I treated experienced severe toxicity during the adjuvant chemotherapy phase. I feel reassured having a negative trial now.

 

[thecarbonionangle]

I think these trial results are important.
Some of you may recall this South American randomized trial that looked at Cis/Gem consolidation post CRT for cervical cancer.
This actually became a trend for a short time and one of the patients I treated experienced severe toxicity during the adjuvant chemotherapy phase. I feel reassured having a negative trial now.

Is cis/gem same as carbo taxol in your mind? That is, a negative carbotaxol study negates a positive cis/gem study?

 

[Palex80]

Is cis/gem same as carbo taxol in your mind? That is, a negative carbotaxol study negates a positive cis/gem study?

You are correct, it's not the same systemic treatment. But still, a negative trial with the standard combination that is used in the metastatic setting turning out negative, is reassuring to me.

 

[evilbooyaa]

Is cis/gem same as carbo taxol in your mind? That is, a negative carbotaxol study negates a positive cis/gem study?

Good question, but the concept of consolidative chemotherapy in the IT era is DEAD. There is some ongoing stuff in this space with I believe Durva a-la PACIFIC, and that will be where the money is.

I had an idea when I first saw PACIFIC presented, to basically replicate PACIFIC literally every single disease site with whichever corporate sponsor is willing to run it. Starting to see it (Esophageal as an example), but it hasn't been as ubiquitious as I would've otherwise expected.

 

[Palex80]

I had an idea when I first saw PACIFIC presented, to basically replicate PACIFIC literally every single disease site with whichever corporate sponsor is willing to run it. Starting to see it (Esophageal as an example), but it hasn't been as ubiquitious as I would've otherwise expected.

Anal cancer is being tested too and looks promising, as far as I have heard (although the bar is already quite high in anal cancer, much more difficult to enhance results than in NSCLC).

 

[Krukenberg]

Good question, but the concept of consolidative chemotherapy in the IT era is DEAD. There is some ongoing stuff in this space with I believe Durva a-la PACIFIC, and that will be where the money is.

I had an idea when I first saw PACIFIC presented, to basically replicate PACIFIC literally every single disease site with whichever corporate sponsor is willing to run it. Starting to see it (Esophageal as an example), but it hasn't been as ubiquitious as I would've otherwise expected.

There are definitely trials in every definitive RT disease site ongoing. They’ll take time but there’s lots of enthusiasm.

 

[ramsesthenice]

There are definitely trials in every definitive RT disease site ongoing. They’ll take time but there’s lots of enthusiasm.

Off hand I can think of H&N, esophagus, cervical, high risk endometrial, anal, rectal, and bladder all ongoing.

 

[Ray D. Ayshun]

Doing adjuvant nivo in esophagus where I am if residual disease at surgery. Didn't realize that had become soc, but apparently so. Which is not to say I'm not a fan.

 

[ramsesthenice]

Doing adjuvant nivo in esophagus where I am if residual disease at surgery. Didn't realize that had become soc, but apparently so. Which is not to say I'm not a fan.

It’s not. Someone must have a deal with one of the companies. They are giving away tons of this looking for any and every indication they can find. It’s only approved for metastatic GEJ/gastric tumors. No adjuvant indications there yet.

 

[Ray D. Ayshun]

It’s not. Someone must have a deal with one of the companies. They are giving away tons of this looking for any and every indication they can find. It’s only approved for metastatic GEJ/gastric tumors. No adjuvant indications there yet.

FDA approves nivolumab for resected esophageal or GEJ cancer

FDA approves nivolumab for resected esophageal or GEJ cancer

www.fda.gov

On NCCN as well now.

 

[ramsesthenice]

FDA approves nivolumab for resected esophageal or GEJ cancer

FDA approves nivolumab for resected esophageal or GEJ cancer

www.fda.gov

On NCCN as well now.

I thought that was still pending. Thanks for sharing.

 

[ramsesthenice]

Anal cancer is being tested too and looks promising, as far as I have heard (although the bar is already quite high in anal cancer, much more difficult to enhance results than in NSCLC).

One of the oncologists in our group is on the alliance steering committee and apparently the results are looking good. No specifics have been shared (as is appropriate) but my gut reaction was the same as yours. LC for all but the bulkiest tumors is already pretty good. As long as they dont have over representation by low volume N1 patients with small primaries they could be ok. I want it to work. We have enrolled several and the only failure we have had was in the control group. Dude had a massive primary so it’s not a shock.

 

[Phantom1]

Cisplatin is the most effective radiosensitizer known. Going to be around for awhile... but remember with chemorads its radiation that is doing 90% of the cure, adding cisplatin helps maybe 10%, but when med oncs give radiosensitizing chemo they act like it is their chemo doing 90% of the work...

 

[evilbooyaa]

Doing adjuvant nivo in esophagus where I am if residual disease at surgery. Didn't realize that had become soc, but apparently so. Which is not to say I'm not a fan.

It’s not. Someone must have a deal with one of the companies. They are giving away tons of this looking for any and every indication they can find. It’s only approved for metastatic GEJ/gastric tumors. No adjuvant indications there yet.

Pretty new data, was presented at ASCO 2021 IIRC? Also pubhlished in NEJM:

https://www.nejm.org/doi/full/10.1056/NEJMoa2032125

Checkmate 577. Only PFS data as of right now, but similar to PACIFIC, people will treat with PFS benefit before OS data has been published.

 

[ramsesthenice]

Pretty new data, was presented at ASCO 2021 IIRC? Also pubhlished in NEJM:

https://www.nejm.org/doi/full/10.1056/NEJMoa2032125

Checkmate 577. Only PFS data as of right now, but similar to PACIFIC, people will treat with PFS benefit before OS data has been published.

I saw the presentation, just didn't see the FDA response yet. Knew it was in the pipeline. From personal experience, felt very good about the chances. I have had a couple patients with concurrent lung and esophageal cancers who got adjuvant durvalumab per PACIFIC and have all done extremely well at both sites. Small number, certainly nothing conclusive, but very encouraging.