#Tweetorial1️
✅Only ~40-60% of GEA pts receive 2L Rx in the USA, & the treatment landscape is fragmented.
📌 https://pubmed.ncbi.nlm.nih.gov/25792290/ 
📌 https://pubmed.ncbi.nlm.nih.gov/31056940/ 
@TumorBoardTues #TumorBoardTuesday
#Tweetorial2
✅The Phase III 2L RAINBOW study of paclitaxel-Ram vs Paclitaxel had improved OS, serving as a benchmark SOC
📌 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70420-6/fulltext
#Tweetorial2The Phase III 2L RAINBOW study of paclitaxel-Ram vs Paclitaxel had improved OS, serving as a benchmark SOC https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70420-6/fulltext
#Tweetorial2The Phase III 2L RAINBOW study of paclitaxel-Ram vs Paclitaxel had improved OS, serving as a benchmark SOC https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70420-6/fulltext
#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)
📌 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31257-1/fulltext
📌 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31257-1/fulltext#supplementaryMaterial
#Tweetorial4
✅Studies show that FOLFIRI is an option vs paclitaxel, along w ramucirumab, in certain situations-
1) persistent oxaliplatin neuropathy or
2) previous Rx with platinum/taxane perioperatively or 1L:
📌 https://pubmed.ncbi.nlm.nih.gov/30470690/ 
📌 https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4514
#Tweetorial4Studies show that FOLFIRI is an option vs paclitaxel, along w ramucirumab, in certain situations- 1) persistent oxaliplatin neuropathy or 2) previous Rx with platinum/taxane perioperatively or 1L: https://pubmed.ncbi.nlm.nih.gov/30470690/  https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4514
#Tweetorial4Studies show that FOLFIRI is an option vs paclitaxel, along w ramucirumab, in certain situations- 1) persistent oxaliplatin neuropathy or 2) previous Rx with platinum/taxane perioperatively or 1L: https://pubmed.ncbi.nlm.nih.gov/30470690/  https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.4514
#Tweetorial5a
✅2L studies were -ve for anti-HER2 Rx in 2L:
📌 Phase 3 TyTAN (lapatinib) https://pubmed.ncbi.nlm.nih.gov/24868024/ 
📌 Phase 3 GATSBY (TDM1) https://pubmed.ncbi.nlm.nih.gov/28343975/ 
📌 Phase 2 T-ACT (trastuzumab) https://pubmed.ncbi.nlm.nih.gov/32208960/ 
Randomized, Phase II Study of Trastuzumab Beyond Progression in Patients With HER2-Positive...

The TBP strategy failed to improve PFS in patients with HER2-positive advanced G/GEJ cancer, and no beneficial biomarkers were found.

https://pubmed.ncbi.nlm.nih.gov/24868024/
#Tweetorial5b
Some contributing reasons for these -ve studies include:
1) Allowed HER2 IHC0/1+ w FISH+ (based on pre-1L profile) (TyTAN = (35%!))
2) Not rechecking HER2 status after PD on 1L Rx (all 3 studies)
✅ A subgroup of T-ACT tumors at just prior to 2L 69% (!) were HER2-
#Tweetorial5c
3) Relatively small studies w ⬇️ power

✅ Despite this, in TyTAN, ORR ITT was 27% vs 9% in favor of pac/lap vs pac,
✅ & in those with pre-1L IHC3+ (who r less likely to evolve to neg @ 2L) --> OS advantage (ORR not reported but likely higher: 40%?, 50%?):
#Tweetorial5c3) Relatively small studies w power Despite this, in TyTAN, ORR ITT was 27% vs 9% in favor of pac/lap vs pac, & in those with pre-1L IHC3+ (who r less likely to evolve to neg @ 2L) --> OS advantage (ORR not reported but likely higher: 40%?, 50%?):
#Tweetorial5c3) Relatively small studies w power Despite this, in TyTAN, ORR ITT was 27% vs 9% in favor of pac/lap vs pac, & in those with pre-1L IHC3+ (who r less likely to evolve to neg @ 2L) --> OS advantage (ORR not reported but likely higher: 40%?, 50%?):
#Tweetorial6️
✅Recent papers evaluating HER2 conversion show rates of conversion between 15-45%.
✅ The longer the pt is on & over more lines of anti-HER2 Rx may increase this finding.
📌 https://pubmed.ncbi.nlm.nih.gov/29122777/ 
📌 https://pubmed.ncbi.nlm.nih.gov/33234578/ 
#Tweetorial7
✅Tras-Derux in Asian phase 2 in 3L+ (~55% 3L, 45% 4L+) showed better ORR, PFS, and OS compared to MD choicetaxane/irinotecan.
📌 https://www.nejm.org/doi/full/10.1056/NEJMoa2004413
📌Approved in Japan for 3L+ 9/25/20
📌Approved by FDA for 2L+ 🤔 1/15/21.
Black Box: ILD, Reassess HER2 bx!
#Tweetorial7Tras-Derux in Asian phase 2 in 3L+ (~55% 3L, 45% 4L+) showed better ORR, PFS, and OS compared to MD choicetaxane/irinotecan. https://www.nejm.org/doi/full/10.1056/NEJMoa2004413 Approved in Japan for 3L+ 9/25/20Approved by FDA for 2L+ 1/15/21. Black Box: ILD, Reassess HER2 bx!
#Tweetorial7Tras-Derux in Asian phase 2 in 3L+ (~55% 3L, 45% 4L+) showed better ORR, PFS, and OS compared to MD choicetaxane/irinotecan. https://www.nejm.org/doi/full/10.1056/NEJMoa2004413 Approved in Japan for 3L+ 9/25/20Approved by FDA for 2L+ 1/15/21. Black Box: ILD, Reassess HER2 bx!
#Tweetorial7Tras-Derux in Asian phase 2 in 3L+ (~55% 3L, 45% 4L+) showed better ORR, PFS, and OS compared to MD choicetaxane/irinotecan. https://www.nejm.org/doi/full/10.1056/NEJMoa2004413 Approved in Japan for 3L+ 9/25/20Approved by FDA for 2L+ 1/15/21. Black Box: ILD, Reassess HER2 bx!
#Tweetorial7Tras-Derux in Asian phase 2 in 3L+ (~55% 3L, 45% 4L+) showed better ORR, PFS, and OS compared to MD choicetaxane/irinotecan. https://www.nejm.org/doi/full/10.1056/NEJMoa2004413 Approved in Japan for 3L+ 9/25/20Approved by FDA for 2L+ 1/15/21. Black Box: ILD, Reassess HER2 bx!
CASE DISCUSSION
👇👇👇
#Tweetorial8a Case Discussion 1/2
✅ CPS 0 (no pembro), per #KN061
✅ ctDNA HER2 -ve (despite PT HER2+) predicts likely failure here systemically. I would use Chemo+Ram as their next best 2L option.
(Welcome comments on this point - let's debate! 😎)
#Tweetorial8b Case Discussion 2/2
✅ tumor biopsies can be useful for reassessing tumor biology:
📌 https://pubmed.ncbi.nlm.nih.gov/33234578/ 
✅ but so can liquid biopsies be useful for reassessing tumor biology, and may better represent the dz in its entirety:
📌 https://pubmed.ncbi.nlm.nih.gov/31427281/ 
#Tweetorial9a
✅ For persistently HER2+ tumors, phase 3 2L studies are ongoing, both requiring retesting to confirm HER2+:
📌 Pac/Ram vs Pac/Ram/Tucatinib/Trastuzumab https://clinicaltrials.gov/ct2/show/NCT04499924
📌 Pac/Ram vs T-DXd https://www.clinicaltrials.gov/ct2/show/NCT04704934?term=DESTINY-Gastric04&draw=2&rank=1
Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction...

Trastuzumab Deruxtecan for Subjects With HER2-Positive Gastric Cancer or Gastro-Esophageal Junction Adenocarcinoma After Progression on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04) -...

https://clinicaltrials.gov/ct2/show/NCT04499924
#Tweetorial9b
*My Opinion: With 10% ILD risk, moving T’Dxd earlier than 3L should require direct large-scale comparison to standard Pac/Ram and most importantly, to other SOC (readily available) as well as investigational anti-HER2 approaches. 🧐
Cheers 🍻and Happy Valentine's💝
SUMMARY:
#targetedtherapiesfortargetedpopulations
Treating with the right drug, at the right dose, at the right time. 😎 #MedTwitter #TumorBoardTuesday
You can follow @DocCatenacci.
Tip: mention @twtextapp on a Twitter thread with the keyword “unroll” to get a link to it.

Latest Threads Unrolled:
Those who think consciousness raising & movement building are disconnected, or even a distraction from electoral politics have not paid attention to the history of social change.In this thread, we
Read more
The 2020s will be known as the Remote Work decadeA few predictions of what is likely to emerge[ a thread ] Third Space: Office and Working from Home will
Read more
1/29: Have you ever had a concept explained to you that helps frame complex issues you’ve been wrestling with and opens your eyes to new possibilities? A concept that I
Read more
By continuing to use the site, you are consenting to the use of cookies as explained in our Cookie Policy to improve your experience.