Daniel Catenacci Profile picture
Jul 10, 2020 6 tweets 5 min read Read on X
So great that HER2+ GEA has many promising new tx’s! The next yrs will be important for us to study how to optimally sequence of all of them to best treat our pts!!
#margetuximab #tras #tucatinib #trasderux #zw25 etc...

#retifanlimab #pembro #nivo etc...

thelancet.com/journals/lanon… Image
In addition to the main text, be sure to check out pages 4-11 of the supplement. Lots of good stuff buried there. Most important to me are the biomarker subgroups analyses: “Targeted therapies for targeted populations!” Some long-term survival noted in the double-positive group. Image
Important observations to me:
1. All observed responses were IHC 3+ at 1L dx.
2. 79% of responses were PDL1 CPS>1 at 1L dx
3. 88% of responses were ctDNA HER2+ at time of enrollment prior to 2L tx on study.
4. ⬆️est response was amongst those with all 3 of those biomarkers+. ImageImageImage
These data generated the hypothesis that a chemo-free dual-AB approach may be effective in these highly biomarker selected pts, which is now being prospectivly tested in the ongoing 1L ‘cohort A’ of the MAHOGANY study! 🤞🏼💪🏼NCT04082364
clinicaltrials.gov/ct2/show/NCT04… Image

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More from @DocCatenacci

Feb 10, 2021
#Tweetorial1️
✅Only ~40-60% of GEA pts receive 2L Rx in the USA, & the treatment landscape is fragmented.
📌 pubmed.ncbi.nlm.nih.gov/25792290/
📌pubmed.ncbi.nlm.nih.gov/31056940/
@TumorBoardTues #TumorBoardTuesday Image
#Tweetorial2
✅The Phase III 2L RAINBOW study of paclitaxel-Ram vs Paclitaxel had improved OS, serving as a benchmark SOC
📌thelancet.com/journals/lanon… ImageImage
#Tweetorial3
✅The Phase III 2L KN061 study showed detriment for pts with PDL1 CPS 0 treated w pembro vs paclitaxel (no Ram!), and terminated this group early.
(green = pembro, red = paclitaxel)
📌 thelancet.com/journals/lance…
📌 thelancet.com/journals/lance… Image
Read 17 tweets
Feb 10, 2021
#TumorBoardTuesday
1/3 CASE: 35 y/o F w stage 4 (diffuse supraclav/RP M1 LNs) GEJ AC, HER2 IHC3+, PD on 1L FOLFOX-trastuzumab after ~12m w new lung&peritoneal dz. Repeat EGD w bx: HER2 IHC3+/CPS 0. ctDNA profile NO HER2 amp (TP53 mt MAF 9.3%).
How would u treat this pt now?
#TumorBoardTuesday
2/3 CASE:35 y/o F w stage 4 (diffuse supraclav/RP M1 LNs) GEJ AC, HER2 IHC3+, PD on 1L FOLFOX-trastuzumab after ~12m w new lung&peritoneal dz. Repeat EGD w bx: HER2 IHC3+/CPS 0. ctDNA PROFILE w/o HER2 amp (TP53 mt MAF 9.3%). PS0
How would u treat this pt now?
3/3: Here’s a f/u related POLL:
Currently my preferred line to use trastuzumab-deruxtecan is:
Read 7 tweets
Sep 24, 2020
Ok...Honeymoon is over & now time to dissect the exciting new data presented @ #ESMO2020 for #GEC #KN590 #CM649 #ATTRCN4 #CM577
1st, thank you to all the pts who participated!
& 2nd, congrats to all the investigators involved!
It's fantastic to have +ve studies! Lets dive deep:
*Caution
I think the facts are accurate - please correct if not. (seeking the truth here)
My opinions are my opinions.
~15 min read (it's complicated)
No CME offered unfortunately 😒😉
Enjoy...
Background:
IO monotx effective in a subgroup of GEC pts in 1L+:
1. MSI-H
2. High PDL1 (cut-off at least CPS 10 22C3)
3. low tumor burden
4. PS0
5. Asian > Western pts
6. SCC > AC
7. GC > EGJ
Outside of above, most pts are better-served w chemo based on crossing #yinyang curves
Read 35 tweets
Aug 19, 2020
It will be important to look at the data closely, particularly by histology. Merck’s KEYTRUDA® (pembrolizumab) in Combination W Chemo Significantly Improved OS and PFS Compared W Chemo in 1L Metastatic Esophageal Cancer | Business Wire businesswire.com/news/home/2020…
We must recall that a ~500 pt study of the exact same regimen KN062 was recently statistically negative (HR0.85 p=0.046) in CPS>0 in adeno. Now the same regimen in KN590 N=749, in all-comers irrespective of PDL1 but including SCC, is +ve. What could be driving this difference?🤔
Let’s see the data: the make-up by histology (& PDL1!) & the benefit magnitude diffs (as might be expected) b/w them before we jump to conclusions on both CM577 and KN590, and also CM649. Let’s not make press releases drive the science! #esmo2020 is going to be a doozy for #GEA!!
Read 6 tweets
Jul 1, 2020
🎶you may say I’m a dreamer...🎶 Overcoming Heterogeneity to Develop Targeted Therapies for Gastroesophageal Cancer prac.co/l/ybw6j8e6 via @practiceupdate @LizzySmyth1 PANGEA2 planning with @KlempnerSam !!
Image
Read 5 tweets

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