Optimizing Maintenance in HER2+ Metastatic Breast Cancer: A thread

🧵 1) Welcome to a new #accredited #tweetorial on HER2+ Metastatic Breast Cancer. This tweetorial provides 0.25 AMA PRA Category 1 Credits. #CME.

2. Before commencign this activty, the statement of accreditation and disclosures can be found at https://app.medall.org/articles/1-l-her-2-hr-mbc-cme-material-and-disclosures This program has been supported by an independent medical education grant from Pfizer and is delivered in joint providership with AffinityCE

So . . . How much do you know about #HER2Positive MBC? 🤔

3. In #HER2Positive MBC, maintenance therapy should sustain disease control while reducing toxicity and improving quality of life. Let’s dive into the shift from CLEOPATRA’s model to current de-escalation trials #MedOnc

4. We asked Prof Mark Pegrum to share his thoughts about how the evidence on HER2+ MBC maintenance evolved from the CLEOPATRA trial to today? 👇

5. What is the role of endocrine therapy ± CDK4/6 inhibitors in HE2R+/HR+ MBC 1L setting?

Well, first it’s important to understand ER/HER2 crosstalk: HER2 signaling confers resistance to endocrine intervention. 💡Growth factor signalling activates ER in the absence of oestrogen via downstream HER2 signal transduction molecules 💡Activated cytoplasmatic ER dimerizes and translocates to the nucleus, induces transcription or ER-dependent genes

6. But interestingly - its bidirectional: ER-pathway as an escape mechanism to HER2-inhibition 💡 HER2 signalling down-regulates ER-regulated transcription – resistance to endocrine therapy 💡 HER2 inhibition results in activation of ER-regulated – compensatory mechanism for tumor growth and survival 💡 Superior inhibition of tumour growth by parallel blockade of HER2 and ER pathways

7. Key Studies: ✅PATINA ✅PERTAIN ✅monarcHER

8. Prof. Rupert Bartsch shared with us a little of the background - Why add CDK4/6 inhibitor therapy in HER2+ MBC?’

9. 💊 #CDK46i in #HER2Positive MBC - #PATINAStudy ✔️ AFT-38 PATINA: #CDK46i as part of 1L maintenance ✔️ #Palbociclib + anti-HER2 and ET 🆚 anti-HER2 and ET ✔️ Improved PFS with #palbociclib (p=0.0074)

10. 💊 #CDK46i in #HER2Positive MBC - #DESTINYBreast07Trial ✔️ #DESTINYBreast07: #T-DXd ± #pertuzumab in 1L #HER2Positive MBC ✔️ PFS rates higher with #T-DXd + #pertuzumab ⚠️ Diarrhea rate higher ✔️ Published Phase 3 DESTINY-Breast09 will provide definitive data

11. 🔎Now let’s explore maintenance in first-line #HER2Positive MBC some more, with somes Cases👇#OncoTwitter #MedOnc

12)❓Which therapy would you choose in this case?

13. Dr Sarah Sammons discussed this case recently at a MedAll Grand Rounds:

14. 🔎What about multidrug maintenance strategies? Let’s look at another case 👇 #CaseBasedLearning #OncoTwitter #MedOnc #ClinicalCase

13. ❓Which therapy would you choose for this patient?

14. In relation to this case, Dr Sarah Sammons explained at our recent grand round the PATINA trial for ER+, HER2+ MBC:

15. Thank you for participating in this tweetorial! We hope you are as excited about the future of #HER2+ MBC as we are!

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