Advertisement - Members don't see this ad
PACIFIC-2 is negative
Started by Palex80
Interesting. Combination of chemo and immunotherapy (without radiation) appears to have been a successful strategy in both small and non-small cell lung cancer.
It is surprising that they also picked PFS as a primary endpoint which was unsuccessful. I look forward to a half dozen additional papers on subset analysis forthcoming.
I certainly haven't kept up with all the phase I/II data as well as most here I'd imagine, but it seems to me that the benefit of immunotherapy may be AFTER radiation, not during it. Maybe localized radiation is killing off the lymphocytes that need to be active when the immunotherapy is ongoing? I'm playing amateur scientist here.
Bingo
This may indeed be so. It may be the reason why the Javelin-Trial was negative in H&N cancer.
Will need to see the full data to see if it was a trial design issue or biology, though the latter would make sense and consistent with all of the failed concurrent IO-CRT studies in HNSCC.
sequential works well in lung, esophagus, cervix and bladder is pending
This may mean the death of neoadjuvant CRT for any indication where immunotherapy may prove beneficial.
Neoadjuvant esophagus CRT may die, simply because neoadjuvant IO+Chemo may be as beneficial (if not superior), and neoadjuvant IO + CRT may not work.
agree unless we start looking at neoadj chemo-XRT, wait 2 weeks or so, then (?chemo?) IO....but then you're pushing out "definitive" surgery more and more....
This line of thought would seem to argue that radiation alone would improve by spacing out fractionation. I guess this is what PULSAR is all about?
It's interesting how confident people are in their analysis of the way the NSCLC world works based on this press release... and I guess prior HN trials 🙂
Concurrent + adjuvant works in cervix per KEYNOTE A18, although negative per CALLAS. Maybe Pembro is the most secret of the sauce out of all the ICIs.
All this means is that SOC remains concurrent chemoradiation followed by Durva in stage III NSCLC.
Until trials are done it is impossible to make definitive statements to other disease sites or other immunotherapy agents.
Last edited:
Advertisement - Members don't see this ad
Last edited:
I’m not sure it’s even news, let alone fake! LOL
I don’t know what it is exactly beyond seeing a few Timmerman slides and a few entries on clinicaltrials.gov
Yep.
I recently accrued someone to S1806 (bladder) and was annoyed to learn that IO given concurrently as well as adjuvantly.
KISS.
D
deleted1111261
What in the world is he saying ?
Anyone else look at those results and think, "meh"?
We need a song from that guy that does the "There I ruined it" that sums up the current fubar state of the world of radonc...
The implication is kinda cool IMO. Does giving IO concurrently diminish the efficacy it has in the adjuvant setting?
Seems like this might be. Either that or Pacific a false positive...seems unlikely given the extent of effect.
The timing of XRT relative to IO may be crazy critical.
Seems like this might be. Either that or Pacific a false positive...seems unlikely given the extent of effect.
The timing of XRT relative to IO may be crazy critical.
Advertisement - Members don't see this ad
Or a lot of other things we don't know yet because press releases are not the same thing as scientific papers.
Actually, the Securities and Exchange Commission likely does a better job than most peer reviewers of scientific journals.
Esophagus (adenocarcinoma) is an uphill battle for radonc.
Once the neoadjuvant IO+Chemo trials read out, we are out of the equation.
Esophagus (SCC) still holds potential. Especially with organ preservation.
HPV .. they tried to fraction/dose shame.
Then it was volume shaming.
But in the end..
Then it was volume shaming.
But in the end..
Data for neoadjuvant IO + chemo in esophagus?
More chemo alone was more toxic and equally efficacious than chemoRT in NEO-AEGIS
More chemo is not always better than chemo and some RT.... see PREOPANC-2
MATTERHORN, Keynote-585, DANTE will soon read out. And the medonc argument will be:
"Since NEOAEGIS showed that radiochemo is as good as chemo, and since those 3 trials showed IO-chemo is better than chemo alone, we can safely abandon radiochemo."
D
deleted1111261
The reality is, we are going to be marginalized with the IO/Chemo Neoadjuvant stuff.
For lung, this has come up. I had a patient - direct from pulm. Has single station N2 (subcarinal) and a hilar mass. On my eval, this has pneumo written all over it. Verbally talked to surgeon and without even looking at images, says "why not IO/chemo then surgery instead of CRT?" I sent NCCN slide showing that this was category 1, and I don't think we should do non-category 1 for our patients and they demurred (academic center). Presented at our local tumor board, medonc says "why not IO/CT? it's limited N2 disease?". I had the radiologist describe the tumor and how it basically wrapped around the mainstem bronchus. "That's going to require a pnemonectomy".
But, if this was T3 because of some other reason, I was going to get out-voted.
Locally, I'm getting the feeling that every IIIA is going to be looked at for the possibility of IO/CT first.
Luckily, at the moment, I am the primary onc for most lung cancers here and I can push a bit for standard of care.
For lung, this has come up. I had a patient - direct from pulm. Has single station N2 (subcarinal) and a hilar mass. On my eval, this has pneumo written all over it. Verbally talked to surgeon and without even looking at images, says "why not IO/chemo then surgery instead of CRT?" I sent NCCN slide showing that this was category 1, and I don't think we should do non-category 1 for our patients and they demurred (academic center). Presented at our local tumor board, medonc says "why not IO/CT? it's limited N2 disease?". I had the radiologist describe the tumor and how it basically wrapped around the mainstem bronchus. "That's going to require a pnemonectomy".
But, if this was T3 because of some other reason, I was going to get out-voted.
Locally, I'm getting the feeling that every IIIA is going to be looked at for the possibility of IO/CT first.
Luckily, at the moment, I am the primary onc for most lung cancers here and I can push a bit for standard of care.
This is my experience as well, though our CT surgeon (specializes in cancer, not a heart surgeon that dabbles in lung cancer) is very good and reasonable. I do often have to remind him that on the pre op trials patients had to be up-front resectable, so I strongly vote against any attempt at "converting" these patients. Also important to note that resectable means BOTH lung parenchymal tumor and nodes are able to be resected...it doesn't help to leave gross mediastinal disease.
So far we have only done neoadj chemo/IO in lobectomy patients. They have mostly done well though some have had minimal response and were borderline for surgery so have had to "convert" back to chemo/XRT.
it has definitely cut into our definitive chemo-XRT volume though.
I do feel like patients with bigger (but still resectable with lobectomy) primary tumors and single station N2 may be the "sweet spot" for that good surgical benefit. Too many though in my community tumor board experience just want to jump into chemo-IO before considering above resectability concerns. I've seen med onc start chemo/IO before patient even seen by CT surg or presented at lung cancer conference.
Advertisement - Members don't see this ad
Our specialty has destroyed itself. Please let me # it out quietly in the hinterlands for another 5 years and I'll call it a wrap.
There is going to be a lot of regional variation and we will get pushed out of some things at some places (or already have 🙁). Though before we push the panic button, there is also the chance that in at least some sites, it is surgery who ends up losing. We already know that surgery doesn't cure many more (if any) patients than primary chemoradiation for stage III NSCLC. Would not be at all surprised if primary chemo RT followed by adjuvant Chemo + IO ended up beating or at least tying either neoadjuvant option plus surgery. Same for esophageal adenocarcinomas. If you can get the pCR up over 50%, the benefit of a highly morbid surgery starts to become more questionable...as has been the case for esophageal SCCs for a while now. Might all be wishful thinking but our demise has been just around the corner for decades. Hopefully the real though leaders in the field do the right trials to keep us in the game.
I think surgery will, in many cases, simply disappear from the menu.. long before radiation.
Question is: what would you rather have.. chemorads or a knife?
Triple Modality gunna mean something different: Chemo/IO + rads.
What a time to be a radonc..
almost all our "limited" stage 3 are sent for chemo/io then surgery
I have pushed back hard on downstaging stage 3 lung and would encourage all to do the same
That was not the intent or inclusion criteria
We didn’t use chemorads to downstage to live tiny either
Lung surgery required is typically not dependent on neo therapies
That was not the intent or inclusion criteria
We didn’t use chemorads to downstage to live tiny either
Lung surgery required is typically not dependent on neo therapies
Its all over but the cryin'
Single station N2 requiring a lobectomy (upfront) was routinely being sent for neoadjuvant chemo (pre-IO data) and surgery at many academic institutions.
Agree with others that chemo/IO should 100% NOT be used to 'converting' someone to resectable. If someone is not resectable at initial diagnosis, they should get chemoRT because even in resectable patients up to 20% of them end up NOT getting surgery due to neoadjuvant chemoIO.
Agree with others that chemo/IO should 100% NOT be used to 'converting' someone to resectable. If someone is not resectable at initial diagnosis, they should get chemoRT because even in resectable patients up to 20% of them end up NOT getting surgery due to neoadjuvant chemoIO.
I think the breast cancer experience is highly informative. We now know that all patients with positive nodes undergoing upfront mastectomy benefit from chest wall and regional nodal RT.
pubmed.ncbi.nlm.nih.gov
That hasn't stopped medical oncology from integrating neoadjuvant chemotherapy - without a documented survival benefit mind you - and then immediately calling into question the role of RT with pathologic complete response.
It doesn't bode well for radiation oncology in any site where surgery is a local option (breast, rectal, lung, pancreas, esophagus).
Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials - PubMed
Cancer Research UK, Medical Research Council.
pubmed.ncbi.nlm.nih.gov
That hasn't stopped medical oncology from integrating neoadjuvant chemotherapy - without a documented survival benefit mind you - and then immediately calling into question the role of RT with pathologic complete response.
It doesn't bode well for radiation oncology in any site where surgery is a local option (breast, rectal, lung, pancreas, esophagus).
That benefit?
In an illustrative calculation, estimated absolute reductions in 15-year breast cancer mortality were 1·6% for women with no positive axillary nodes, 2·7% for those with one to three positive axillary nodes, and 4·5% for those with four or more positive axillary nodes.
Its amazing anyone gets RNI these days given the overwhelming use of immunotherapy.
?
Not sure about the connection.
BTW, event free survival benefit of pembro in Keynote 522 was 4.4%
Advertisement - Members don't see this ad
I think the breast cancer experience is highly informative. We now know that all patients with positive nodes undergoing upfront mastectomy benefit from chest wall and regional nodal RT.
Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials - PubMed
Cancer Research UK, Medical Research Council.
That hasn't stopped medical oncology from integrating neoadjuvant chemotherapy - without a documented survival benefit mind you - and then immediately calling into question the role of RT with pathologic complete response.
It doesn't bode well for radiation oncology in any site where surgery is a local option (breast, rectal, lung, pancreas, esophagus).
Completely different disease sites - neoadjuvant chemo in breast is most common in Her2+ and TNBC (widespread use of it in Luminal-A patients is silly) and those two subgroups have very good pCR or near pCR rates, certainly resulting in a higher percentage of patients NOT requiring a mastectomy compared to upfront resection.
B51 will provide some guidance when it results about randomized safety of omission, but some (not good as I initially posted) data from B27.
In lung cancer we had poor quality data that RT to pN1+ NSCLC patients who receive chemo is BAD and same data suggesting RT in pN2+ NSCLC patients was good, which was then superceded by a randomized trial which (globally) said adj. RT in N2 NSCLC is unnecessary. Yes, yes, 3D vs IMRT, lower risk of LR, etc. etc., but no OS advantage which is what people are looking for. So saying that "PMRT is good, thus post-surgery RT in NSCLC is good" isn't really EBM.
The analogy is that chemoRT is the standard for almost all NSCLC patients with N2 nodal disease at least in the community. Neoadjuvant chemotherapy alone did not significantly move the needle.
Chemo IO comes along and now medical oncology and thoracic surgery are clamoring for trying neoadjuvant on most patients with lower volume N2 nodal disease. In the setting of neoadjuvant chemoRT, RT is generally relegated to salvage or inability to undergo surgery thus loss of market share.
Neoadjuvant therapy seems to have an amazing skill at diminishing the role for RT, even in evidence-based indications like post-mastectomy radiation for patients with positive lymph nodes. Patients with initially node positive disease from triple negative breast cancer with pathologic CR at mastectomy have declined RT when that would not have happened if they underwent upfront surgery.
Certainly a worrisome trend across disease sites without getting into PROSPECT for rectal or FOLFIRINOX for pancreatic.
You should probably get that checked out! Sounds horrifying.
Because the track record for this is so good lol
Maybe in europe
It’s only really been asked in rectal and it’s funny you bring up Europe. Because it’s the European, not American surgeons, who still resolutely view rectal as a surgical disease. This is one place where academic centers are actually helping. Many (probably most) high volume centers are almost exclusively proceed with TNT and selective w/w even post PROSPECT.
Let’s not be naive though…rectal is a bit of a special case. Colorectal surgeons operate on true colon cancers 4:1 compared to rectal cancers. Getting them to even ask the question (let alone adopt a new paradigm) will be very different than most other disciplines. The bar is different
Seems very institutional dependent though. Most have been progressive about attempting TNT/organ preservation. Anecdotally I’ve seen aggressive adoption of omission of XRt/Prospect zealots from MSKCC in my patients getting opinions there.
MSKCC is an interesting place for rectal which is no surprise. They were very aggressive early on with regards to TNT and selective omission of surgery. They also played a fairly big role in PROSPECT. It’s a huge center with different camps. I won’t name anyone specific but I recently had a detailed discussion about practice patterns with a member of their GI team and overall it appears to come down to the preference of who you meet first. Which…is pretty depressing in a way. I thought the point of going to leading centers was to have more options. Alas…
I don’t like to presume to know why anyone does or says what they do, but I struggle a lot to give too much benefit of the doubt on this one. We have actually offered PROSPECT approach for lower risk patients in select cases for a while. I can only recall a very small number of times patients opted to take the surgical route even though we very clearly tell them the chances of avoiding radiation with the PROSPECT route are much higher than the chances of avoiding surgery with TNT. Doesn’t matter. We had to close good trials because they were designed pre w/w and they mandated surgery. Accrual absolutely died because no one would agree to commit to surgery regardless of treatment response. Based on my personal experience, it is hard for me to believe when presented in an unbiased way, a substantial proportion of patients would accept surgery to avoid radiation for rectal cancer.
I try hard not to get into med onc bashing mainly because some of my best friends are med oncs and fortunately in my neck of the woods, they mostly shrugged at PROSPECT. But it’s hard not to dismiss the glaring double standard by some. It’s absolutely fair to say the trial showed that select patients with good responses to chemo who have surgery don’t have a local control benefit with radiation. Yet when the chemo trials suggested adjuvant chemo after chemorads and surgery may not improve survival or distant disease control, what was the response?
I hadn't really thought about the above - it is interesting that some how both OPRA and PROSPECT came out of the same institution. Two *very* different paradigms, enrolling potentially the same patient cohorts...
I’ve seen a couple very complex GI patients seen there and not get a multi-d evaluation
Whoever saw them first treated and didn’t even get opinions from colleagues . And these were true multi d cases .
Advertisement - Members don't see this ad
