Thread by @MPishvaian

@TumorBoardTues @JohnEbbenMDPhD #TumorBoardTuesday
📣Welcome as we summarize some of the incredible data from #ASCO23
👉There was SO much to take in, that even focusing on GI Cancers was a challenge
🙏As always, these were the🧑‍🏫that caught OUR interest, but this is not a judgement on those we do not highlight‼️

@TumorBoardTues @JohnEbbenMDPhD 1/21
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🤔Speaking for myself, @knutjla ‘s data has shaken my practice the most (including twice last week)
👉He presented the NORPACT-1 trial of peri-operative FOLFIRINOX vs. upfront🔪for resectable #PancreaticCancer

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer 2/21
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✅@knutjla🗣️a well designed, well run trial
✅The authors even hypothesized a 20%⬆️in mOS
➡️However, pre-operative chemotherapy led to a significant⬇️in 18 month mOS😲
👉Despite a much better R0 resection rate

🤔What are your thoughts💭❓

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao 3/21
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✅The other trial that hopefully can shake things up is @BenWestphalen 's FOOTPATH trial

👉Last year, we saw the SEQUENCE data demonstrated a significant⬆️in mOS for #PancreaticCancer with alternating gem-nab and FOLFOX, compared to gem-nab alone👇

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao 4/21
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✅@BenWestphalen designed a trial to see if alternating the NAPOLI-1 regimen with FOLFOX could improve PFS over gem-nab as first line Tx for #PancreaticCancer

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao 5/21
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➡️@BenWestphalen showed that sequential NAPOLI/FOLFOX led to (over gem-nab-pac):
👉An improved PFS
👉Numerically greater OS
👉Greater tolerability

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao 6/21
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🤔Maybe the 11 mo mOS w/ NAPOLI/FOLFOX is↔️to the 11.1 mo mOS w/ NALIRIFOX (@EileenMOReilly see below)❓
👉BUT NAPOLI/FOLFOX was quite well tolerated

🤔Maybe INTEGRATED SEQUENTIAL NAPOLI/FOLFOX is just a better way to give these3⃣agents❓

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly 7/21
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🤔ORRRR.....maybe NAPOLI/FOLFOX is a way for us to finally give a FFX-like regimen in the2⃣nd line after1⃣st line gem-nab❓

Would you consider INTEGRATED SEQUENTIAL NAPOLI/FOLFOX in the2⃣nd line after1⃣st line gem-nab❓

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly 8/21
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✅Some of the exciting NOVEL data🗣️at #ASCO23 in #PancreaticCancer was with KRAS🎯💊

➡️@DrShubhamPant🗣️ an update on 57 Pts (21 w/ PDAC) Txed w/ the KRASG12C⛔️adagrasib
👉ORR 35% overall
👉N/V/D in ~50% of Pts - almost all Grade ≤2
👉6% Gr 3 fatigue

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant 9/21
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✅@EileenMOReilly gave us our first👀at a KRAS vaccine
➡️ELI-002 is a KRASG12D/R & TLR-9🎯vaccine
➡️Only MRD Pts were eligible - i.e.🚫disease on🖥️, but ct🧬/biomarker➕

➡️The vaccine showed surrogate efficacy
👉77%⬇️in the marker
👉32% clearance of ct🧬

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant 10/21
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✅KRAS⛔️can be effective
👉 But the effect may be short lived

🤔Perhaps there will be⬆️outcomes with combination therapies❓

➡️Drillon, et al showed activity of a SHP2⛔️but only in combos
👉 E.g. SHP2i + encorafenib + cetux in a BRAFV600E mutated CRC

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant 11/21
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✅In #cholangiocarcinoma @DrShubhamPant & Dr. Nakamura🗣️exciting data on HER2🎯💊
👉Tx w/ tucat+trastuz➡️a 47% ORR in 30 Pts
&
👉Zanidatamab➡️a 41% ORR in 80 Pts

✅Giving us two new options for these patients that we might be able to use in sequence❓

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant 12/21
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➡️Dr. Ying🗣️that adding anti-PD1➕anti-VEGF mAbs⬆️PFS in advanced BTC
👉BUT, AEs were⬆️with 4💊Tx
👉This is consistent with the ImBrave151 trial

🤔Stay tuned for OS data

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant 13/21
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➡️Dr. Agrawal🗣️that Chemo☢️for Pts w/ locally advanced GB cancer after gem-cis X 4 cycles improved mOS (10mos) vs observation (4 mos)
🤔BUT with 13% ☢️-induced liver disease, and 6% with a fatal GI bleed

✅This probably doesn’t change our paradigm yet

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant 14/21
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➡️For Claudin 18.2➕G/GEJ cancers, Dr. Xu🗣️in the GLOW trial that that zolbetuximab added to CAPOX⬆️mOS (14.4mos) compared to only CAPOX (12.2mos)
➡️This is consistent with the SPOTLIGHT trial
➡️This should solidify FDA approval for zolbetuximab (IMHO)

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant @KoheiShitara @DrKelseyKlute @ILSONDavid @kspencer725 15/21
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➡️Adding nivo to chemo⬆️OS in mG/GEJ Ca
➡️1y of adj nivo⬆️OS in Pts w/ E/GEJ Ca after chemo☢️
🤔What about post-op nivo for GASTRIC Ca❓

Dr. Terashima🗣️that for Pts w/resected gastric/GEJ Ca nivo added to adjuvant chemo did NOT⬆️3y relapse-free nor 3y OS

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant @KoheiShitara @DrKelseyKlute @ILSONDavid @kspencer725 @YJanjigianMD @mdmanishshah 16/21
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➡️Finally, moving on to the management of advanced #colorectalcancer & rectal Ca, which is getting very complicated😲

➡️First, Dr. Antoniotti 🗣️an update of the AtezoTRIBE trial in which patients with mCRC were randomized to FOLFOXIRI-Bev +/- Atezo

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant @KoheiShitara @DrKelseyKlute @ILSONDavid @kspencer725 @YJanjigianMD @mdmanishshah 17/21
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✅The authors had shown B4⃣ that atezo⬆️mPFS
➡️Now this was also true in dMMR and TMB-H Pts (as expected)
😲BUT in pMMR/Immunoscore-IC High Pts also had an⬆️mPFS & mOS w/ atezo
🤔Perhaps defining ANOTHER subgroup of Pts to benefit from IO in CRC❓

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant @KoheiShitara @DrKelseyKlute @ILSONDavid @kspencer725 @YJanjigianMD @mdmanishshah @ChiaraCrem1 18/21
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✅Dr. Jensen 🗣️the NeoCol trial in CRC, and similar to the NORPACT-1 trial above in PDAC, Pts with resectable CRC were randomized to surgery vs. neoadjuvant chemo
➡️But pre-op chemo did NOT⬆️Disease-free survival nor OS

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant @KoheiShitara @DrKelseyKlute @ILSONDavid @kspencer725 @YJanjigianMD @mdmanishshah @ChiaraCrem1 19/21
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✅To put the PROSPECT trial in context, Dr. Conroy🗣️the PRODIGE 23 trial of TNT with FOLFIRINOX vs. Chemo☢️ for rectal
➡️TNT⬆️Disease-free survival compared to Chemo☢️
&
➡️TNT⬆️OS compared to Chemo☢️

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant @KoheiShitara @DrKelseyKlute @ILSONDavid @kspencer725 @YJanjigianMD @mdmanishshah @ChiaraCrem1 20/21
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🥁roll please...
✅Dr. Schrag🗣️the LONG awaited PROSPECT trial, which was designed on the premise that rectal Ca Pts could be cured WITHOUT pelvic☢️
➡️Pts were randomized to TNT (with FOLFOX) vs. Chemo☢️
➡️BUT Pts w/ a good response to chemo were SPARED☢️

@TumorBoardTues @JohnEbbenMDPhD @knutjla @MDAkhilChawla @FlavioRochaMD @NbmerchantMD @MadameSurgeon @NirajGusani @TsengJennifer @CentralParkWMD @BenWestphalen @mnoel3232 @benweinbergmd @rachnatshroff @mkatzmd @aparna1024 @anup_kasi @AJacomeMD @FogacciJoao @EileenMOReilly @DrShubhamPant @KoheiShitara @DrKelseyKlute @ILSONDavid @kspencer725 @YJanjigianMD @mdmanishshah @ChiaraCrem1 21/21
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✅The trial DID meet its primary endpoint‼️
➡️TNT with SELECTIVE☢️ was NON-INFERIOR to chemo☢️for DFS
➡️And for OS

➡️Interestingly, the PathCR rate was similar with TNT with SELECTIVE☢️ as with chemo☢️
👉 But ONLY 9% of Pts in the TNT arm received ☢️