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Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized Treatment Strategy for Metastatic Disease cancerdiscovery.aacrjournals.org/content/early/…
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Daniel Catenacci
1.9K posts
Daniel Catenacci
@DocCatenacci
Medical Oncologist. "Targeted therapies for targeted populations”
Chicago, IL Katılım Haziran 2014
371 Takip Edilen2.9K Takipçiler
@fernandbteich Yes, I would probably for ESCC, especially for higher PDL1 (like >10) although your point is quite valid.
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@DocCatenacci Would you use it in ESCC with CPS>1? It's still a question of early vs late use at relapse for me. CM577 failed to answer that. Time to have serious periop IO/CRT or neoadjuvant chemo/IO trials in ESCC. There are many reasons to believe preop IO is more effective than adjuvant IO
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#CM577
If only we could have known years ago, maybe we could’ve spared all those patients ineffective (worse than nothing?), toxic expensive therapy.
Daniel Catenacci@DocCatenacci
#CM577 there is no benefit (especially CPS0) in CPS low/neg tumors. 44% of pts. And this is not even by histology which would make adenocarcinoma look even worse. Why is this buried in the supplement? & Why would you give this drug for a year to people having no benefit?
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@fernandbteich First, #CM577 should be considered obsolete anyway for adenocarcinoma due to #ESOPEC & #MATTERHORN.
But yes, OS in CM577 would be even less impressive if the control arm actually got SOC antiPD1 in first line at recurrence when appropriate (ie PDL1+ and or MSI-H).
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@DocCatenacci 💯
I don't even think adjuvant nivo will cease to exist. People are using subgroup analyses to still have a reason to use it. ESCC. CPS>1%. Last time I checked if p>0.05, if we repeat this experiment again, we may have similar OSes. Also control arm with 14% only receiving PD1?
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@fernandbteich Oh sorry I misunderstood your comment ‘drawing the line’. Yes, rather than requiring proof before doing certain treatments, some do it until it is disproved 10 times before it is stopped, maybe.
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@DocCatenacci We used to require 2 decent phase III RCTs with statistically significant endpoints to get a drug approved. Now we're accepting drugs based on ORR in a single phase II and we're even ignoring p-values>0.05 calling a prolonged OS "numerically meaningful" and p-values "irrelevant"
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@PiessenG @MagnusNsurgonc Those numbers are DFS.
If you’re just looking at the numbers, would you rather live (OS) 39.2 months or 52.8 months? 🤔👇🏼
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@DocCatenacci @MagnusNsurgonc But when you considère tps which was a stratification criterion there was some benefit. Addtionaly Even if it not statistically significant i prefer to live 16 months than 11
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#CM577 there is no benefit (especially CPS0) in CPS low/neg tumors. 44% of pts. And this is not even by histology which would make adenocarcinoma look even worse. Why is this buried in the supplement? & Why would you give this drug for a year to people having no benefit?
Joao Fogacci@FogacciJoao
@pashtoonkasi @NEJM @OncoAlert @sitcancer @DocCatenacci @GIcancerDoc @agrothey @EileenMOReilly @AnwaarSaeed3 @marklewismd @ILSONDavid @HH_Oncodr @KlempnerSam 💡Some OncGI fellows have pointed: ➡️Supplementary Appendix: 📌 CPS PDL1 =/> 5 (371 pt): 29.4 ❌ 10.2 m 📌 CPS PDL1 <5 ( 295 pt) : 16.3 ❌ 11.1 m
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@fernandbteich Where to draw the line to what is called HER2+ for trastuzumab? Why is the FISH ratio of 2 used, not 1.9 or 2.5? Or Claudin18.2+ for zolbetuximab why is 2+ in 75% of cells used? They are not perfect either, but it is done, which is better than giving those drugs to everybody.
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@DocCatenacci We're still twisting reality. "Numerically meaningful". 😩
Where do we draw the line?
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Daniel Catenacci@DocCatenacci
@LizzySmyth1 HR 0.78 NS per the presentation but not in the paper (rather HR 0.99 <12m HR 0.67) >12m) Where have we seen this tuning fork curve before? ~1/3 pts no diff. CM577 I think it’s a good idea to see the results by PDL1 1, 5, 10: will likely show same thing as all previous studies
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@LizzySmyth1 HR 0.78 NS per the presentation but not in the paper (rather HR 0.99 <12m HR 0.67) >12m)
Where have we seen this tuning fork curve before? ~1/3 pts no diff. CM577
I think it’s a good idea to see the results by PDL1 1, 5, 10: will likely show same thing as all previous studies
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@DocCatenacci The OS data are not yet mature.
Too few events at this time.
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#ASCO25
⛰️MATTERHORN - first ever randomised trial to show a significant benefit for ICI (or any targeted therapy) in operable gastroesophageal cancer.
~10% ⬆️ EFS at 2y
EFS is important in a disease where metastases cause real morbidity
Happy for my patients!
NEJM@NEJM
Presented at #ASCO25: In resectable gastric and gastroesophageal junction cancer, adding durvalumab to perioperative chemotherapy improved event-free survival and pathological complete response, with no major increase in high-grade adverse events. Full MATTERHORN trial results: nej.md/437IXTF
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@LizzySmyth1 🦗🦗
I just read the paper.
Can you please tell me the HR for OS in the ITT full analysis population? I can’t find it!
Any reason you can think of that HR results for OS (not just EFS) of ITT & by PDL1 <1, <5, or <10 aren’t in the publication or the supplement?
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@SalemGIOncDoc For sure. And for 5-9. But let’s take the small victories when they come!
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Well… it doesn’t fully resolve the issue. The problem also involves the CPS score 1 to 4.
Daniel Catenacci@DocCatenacci
Better late than never, I guess.
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Better late than never, I guess.
Lizzy Smyth@LizzySmyth1
📢 FDA ODAC gets it ✅️ for patients Immune checkpoint inhibitors are a PD-L1 targeted 🎯 therapy in GEA. No target, no efficacy. Let's focus on: ➡️ alternative targets (CLD 18.2, FGFR2b, MTAP...) ➡️ overcoming immune evasion (bispecifics, T-cell engagers, CAR-T..)
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The more I hear about the SANO trial the more worried I become. This is not going to end well. #isde2024
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@aysegulilhanmut MSS. For MSI-H, for me, it remains to be seen if it should be IO alone or IO+chemo.
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@DocCatenacci For ‚all’ GEA patients or for MSS GEA patients?
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#TOPGEAR @ESMO2024
- periop chemo +/- RT for #GEA
- no benefit adding RT
- now 6 Phase 3 studies w/o CRT benefit vs or added to neoADJ/ADJ tx for GEA:
- CRITICS, ARTIST1, ARTIST2, neoAEGIS, ESOPEC, TOPGEAR
- SOC is periop #FLOT for all GEA
Lizzy Smyth@LizzySmyth1
Time to move away from radiotherapy in operable GEA #ESMO24 TOPGEAR ➡️ no survival benefit when RT added to periop chemo TOPGEAR + ESOPEC : both great trials with a definitive answer = no more RT ✅Great drugs in development - let's focus on systemic Rx for cure @myESMO
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Daniel Catenacci retweetledi
🚨PRODIGE23🚨
Long term results now published!
T3-4 rectal adenocarcinoma
Randomized:
CRT➡️🔪➡️FOLFOX
mFOLFIRINOX ➡️ CRT➡️🔪➡️FOLFOX
✅✅✅Improved OS!!!
Looking forward to JANUS clarifying if TNT with FOLFIRINOX vs. FOLFOX improves cCR and/or DFS/OS
pubmed.ncbi.nlm.nih.gov/38986769/
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Already Approved in Japan 3/26/24. Different manufacturing sites for the two countries hopefully??
astellas.com/en/system/file…
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#SPOTLIGHT #GLOW #Zolbetuximab #Vyloy
"Zolbetuximab BLA resubmitted 5/9/2024, after CRL issued on 1/4/2024 by FDA due to 3rd-party manufacturer deficiencies seen during the pre-license inspection of the facility." Target Action Date: 11/9/2024
newsroom.astellas.us/2024-05-30-U-S….
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