Thread by @TumorBoardTues

#TBTWebinar is back ‼️
🥼 @MPishvaian @BreastCancerMD1 @Latinamd @BenWestphalen

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Supported by AstraZeneca Pharmaceuticals & Daiichi Sankyo, Inc

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#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️HER2 activity requires receptor dimerization
✅HER1 = EGFR
✅HER3, HER4

➡️HER2 is frequently overexpressed in multiple cancers
✅Protein⬆️due to gene🧬 amplification
✅Constitutive activation due to activating🧬mutation

#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️HER2 (ERBB2) alterations occur in multiple cancer types
✅Breast Ca 25%
✅Gastric Ca 22%
✅GE jxn Ca 32%
✅CRC 5%
✅Lung Ca 6 to 30%
✅Biliary Ca 5 to 20%

🤔There is some disease specificity re: overexpression vs activating🧬mutation

#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️MOA of Targeted Agents🎯
✅Anti-HER2, eg, trastuzumab🚫signaling
✅Anti-HER2, eg, pertuzumab🚫dimerization
✅Antibody-drug conjugate (ADC), eg,T-DM1 intracellular cytotoxic💊deliv
✅Tyrosine kinase (TK) inhibitor, eg, neratinib🚫activity

#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️There are many HER2 🎯 targeted agents
(Including trastuzumab, pertuzumab, and lapatinib)

➡️These are some of the newer agents
✅Trastuzumab emtansine (T-DM1)
✅Trastuzumab deruxtecan (T-DXd)
✅Margetuximab
✅Tucatinib
✅ARX788

#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️Recent Ph3 trials of HER2🎯Tx in breast Ca

➡️DESTINY-Breast03
✅T-DXd v T-DM1
👉ORR 79% v 34%
👉12 mo OS 94% v 86% P=.007

➡️SOPHIA
✅Margetux+chemo v trastuz+chemo
👉ORR: 25% v 14%
👉mPFS: 5.7 v 4.4 mos P=.001

pubmed.ncbi.nlm.nih.gov/33480963/

#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️Key Ph2 trials of HER2🎯Tx in Gastric/Esoph Ca

➡️My Pathway
✅Trastuzumab + pembrolizumab
👉ORR 91%‼️
👉mOS 27 mos

➡️DESTINY-Gastric01
✅T-DXd vs chemotherapy
👉ORR: 51% vs 14%
👉mOS: 13 v 8 mos P=.01

pubmed.ncbi.nlm.nih.gov/32469182/

#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️Key Ph2 trials of HER2🎯Tx in #CRC

➡️HERACLES
✅Trastuz+lapat
👉ORR 30%

➡️MyPathway🛣
✅Trastuz+Pertuz
👉ORR 32%

➡️MOUNTAINEER🏔
✅Trastuz+Tucatinib
👉ORR 55%

➡️DESTINY-CRC01
✅Trastuzumab deruxtecan
👉ORR 45%
pubmed.ncbi.nlm.nih.gov/33961795/

#TumorBoardTuesday HER2 #TBTWebinar 🔑
Ph2 trial of HER2🎯Tx in Biliary cancer

➡️MyPathway
✅Trastuzumab + Pertuzumab
👉ORR 23%

pubmed.ncbi.nlm.nih.gov/34339623/

#TumorBoardTuesday HER2 #TBTWebinar 🔑

➡️Ph2 trials of HER2🎯Tx in Lung cancer🫁

➡️Basket trial 🧺
✅Trastuzumab emtansine
👉ORR 44%

➡️DESTINY-Lung01 🫁
✅Trastuzumab deruxtecan
👉ORR 55%
👉DCR 92%
👉mOS 17.8 mos

pubmed.ncbi.nlm.nih.gov/34534430/

#TumorBoardTuesday HER2 #TBTWebinar 🔑

Ph2 trial of HER2🎯Tx in Salivary cancer
➡️MyPathway
✅Trastuzumab + Pertuzumab
👉ORR 60%

pubmed.ncbi.nlm.nih.gov/32067683/

#TumorBoardTuesday HER2 #TBTWebinar 🔑
🔑Take home🏡points:
➡️HER2 is overexpressed/activated in many cancers
👉Worse prognosis

HER2🎯Tx has made a major impact:
✅Breast Ca
✅Gastric/GEJ Ca
✅CRC
✅Lung Ca
✅Biliary Ca
✅Salivary Ca

Several🗝️Ph3 trials in motion

HER2 #TBTWebinar #OncTwitter

🙏for joining #TumorBoardTuesday HER2/3 series❗️

🙏#EmanuelPetricoin @PancPathologist @ErikaHamilton9 @BreastCancerMD1 @Latinamd @BenWestphalen @MPishvaian for being our experts‼️

🆓HER2🧬Resources 👉integrityce.com/HER2resources

HER2 #TBTWebinar #OncTwitter #PancreaticCancer

Our next #TumorBoardTuesday discussion details:

🗓𝙉𝙀𝙓𝙏 𝙒𝙀𝙀𝙆 03/01/22

👨🏽‍⚕️@nanudasmd talks #PanCan NETs

📱Right here on our feed!!