Thread by @TumorBoardTues

1/12 #TumorBoardTuesday
2L treatment in #HER2+ breast cancer #MBC is 🤯! @PTarantinoMD led us through latest evidence👩‍⚖️

➡️Here's the Thurs Case🎀
👉Grab🆓 #CME credit by answering quick❓
ALL CME 🔗: integrityce.com/tbt
CME rationale🔗: bit.ly/3NnreMW
Here we go!

2/12 #TumorBoardTuesday
Thurs Case🎀

Take🏠messages:
⬆️ options to tx HER2+ #MBC
✅T-DXd >T-DM1 in 2L setting (DESTINY BREAST-03)
✅Beware ADC tox- think 🫁pneumonitis & GI w T-Dxd
✅ADC design is 🗝:
➡️Need to consider DAR, linker, ability to cause ADCC
✅ADC + IO= open ❓

3/12 #TumorBoardTuesday
Thurs Case🎀

Take🏠messages (cont’d):
✅T-DXd active against brain mets (TUXEDO-1)
✅Triplet (tucatinib, cape, tras) also active in brain mets
✅Next up: T-DXd in HER2 LOW- trials ongoing

📚We captured the discussion here:
twitter.com/i/events/15226…

4/12 #TumorBoardTuesday
Thurs Case🎀

@PTarantinoMD presented a case of a 48 yo 👩extensive 🫁 nodules and 4 cm breast mass.
Prelim molecular (IHC): ER, PR negative; HER2 3+.

Good PS, no substantial med hx/comorbidities

➡️What tx in 1L?

5/12 #TumorBoardTuesday
Thursday Case🎀

😱Progression after THP (PR for 9 months!)
🤔What now❓

💡@MPishvaian raises a good pt re: need to re-test HER2 at first recurrence.

📌Up to 20% of cases tx w anti-HER2 agent
➡️HER2 ⬇️

🙏 Our pt still HER2+. What do we choose now?

6/12 #TumorBoardTuesday
Thurs Case🎀

👉🏽 ADCs have changed #HER2 paradigm in #MBC
DESTINY BREAST-03 🟰 T-DXd vs T-DM-1 in 2L
🔷 T-DXd PFS= 75%
🔷 T-DM-1 PFS= 34.1%

📌 OS data not substantially different
📌 may need more time to see mOS changes

7/12 #TumorBoardTuesday
Thurs Case🎀
❓Why does T-DXd outperform T-DM1?
💡Insights from ADC design

T-DXd= ⬆️conjugated drug, different linker ➡️more drug released= Bystander effect (kills neighboring HER2 LOW or NEG cells)
researchgate.net/publication/34…

h/t @RenoHemonc

8/12 #TumorBoardTuesday
Thursday Case🎀

T-DXd vs T-DM1 have different:
🔷Payloads
🔷Drug antibody ratio (DAR)
🔷Linkers
=
Different toxicities

🫁Pneumonitis relatively common:
T-DXd (10-15%)

Most low grade with ability to re-dose T-Dxd after resolution

9/12 #TumorBoardTuesday
Thurs Case🎀

Why? Deruxtecan payload alone 🚫 cause pneumonitis, but ADC does. Hypothesis= alveolar macrophages are activated

🗝️If G1 pneumonitis resolves in less than 28d
📌re-challenge= same dose;
📌if >28d, ⬇️dose

10/12 #TumorBoardTuesday
Thurs Case🎀

Up to 50% of pts w HER2+ #MBC develop 🧠mets

ADC activity here is a 🗝️❓

TUXEDO shows activity of T-DXd in both stable & active 🧠mets.

📊This great table shared w us by @OncBrothers created by @angela_toss provides a great summary

11/12 #TumorBoardTuesday
Thurs Case🎀
Pt has ongoing response to T-Dxd!
🙏New 2L options for #HER2+ #MBC; 3L SOC unclear
🤔Will SOC change w⬆️data on IO & combo tx?
HER2 LOW data expected soon

12/12

➡️Join us on 05/24/22: @Latinamd & @GDutcherMD take us through management of METex14 #NSCLC😀

Remember #TumorBoardTuesday continues to offer AMA & now MOC credit for FREE! Don’t forget to answer the polls👇🏽
Then click this link to easily request your credit!
ALL CME eval🔗: integrityce.com/tbteval

CME rationale🔗: bit.ly/3NnreMW

https://twitter.com/tumorboardtues/status/1526733009197617152?s=21&t=gSng_FJP0Qw5KMYyHInyig

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