Thread by @drteplinsky

1/22 #TumorBoardTuesday #OncTwitter

60yo 👩🏻‍
ER+/PR-/HER2 low met #BreastCancer
Since 2016: 3 lines of endocrine therapy including AI+CDK 4/6 inhibitor ➡️ Fulvestrant ➡️ Everolimus+exemestane
No actionable mutation

🤨 What would be your first chemotherapy choice:

2/22 #TumorBoardTuesday @MPishvaian @JohnEbbenMDPhD #BreastCancer #BCSM

2021*: Started on capecitabine for 8 months until POD
2022: Switched to paclitaxel for 5 months ➡️ POD in the liver and pleura

🤨 What would be your next step?

3/22 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 1

📌What is HER2-low?

🔸Traditionally HER2-positive and HER2-negative were separate entities
🔸NOW, HER2-low is a separate entity 👉🏽 1+ or 2+ on IHC and ISH negative‼️

📚@PTarantinoMD @curijoey @stolaney1 aacrjournals.org/cancerdiscover…

4/22 #TumorBoardTuesday #BreastCancer
👩🏻‍🏫Mini tweetorial 2

📌HER2-low

🔸Approx 60% of patients who were previously HER2-negative can now be classified as HER2-low‼️
🔹New treatment option for HER2-low as per ✨Destiny-Breast 04 ✨

5/22 #TumorBoardTuesday #BreastCancer
👩🏻‍🏫Mini tweetorial 3

✨ Destiny-Breast 04 (DB-04)✨

🔸Randomized, open-label
🔹HER2-low pts w/ unresectable and/or MBC rx w 1-2 prior lines of chemo (in metastatic setting)
🔸HR+ pts included were considered endocrine refractory

6/22 #TumorBoardTuesday #BreastCancer
👩🏻‍🏫Mini tweetorial 4

✨ Destiny-Breast 04 (DB-04)✨

🔹Pts Randomized to T-DXd (n=373) or TPC (Cape, eribulin, gem, paclitaxel or nab-paclitaxel) (n=184)

📚Modi S @NaokiNiikura @prat_aleix
@NEJM nejm.org/doi/full/10.10…

7/22 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 5

✨Destiny–Breast 04✨

📌Results
👍🏽T-DXd improves PFS in all pts (HR 0.5) 9.9 mo v 5.1 mo TPC (HR+ pts 10.1 mo v 5.4 mo, HR 0.51)
👍🏽T-DXd improves OS in all (HR 0.64) 23.4 mo v 16.8 mo TPC (in HR+ pts 23.9 mo v 17.5 mo HR 0.64)

8/22 #TumorBoardTuesday #MBC #BCSM
👩🏻‍🏫Mini tweetorial 6

✨Destiny-Breast 04✨

📌Results

🎉Based on results - T-DXd approved as first 🎯 therapy for HER2-low unresectable and/or metastatic #BreastCancer in 8/2022 #MBC

9/22 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 7

✨Destiny-Breast 04✨

📌Results
🧐What about HR-/HER2-low?

📍Exploratory endpoints
T-DXd improves PFS (8.5 mo vs 2.9 mo, HR 0.46) and OS (18.2 mo vs 8.3 mo, HR 0.48)

10/22 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 8

🧐Does T-DXd work in all subgroups?
Analyses presented at #SABCS22
T-DXd is effective regardless of:
✅dz burden: ≥3 met sites
✅prior CDK 4/6i/rapid progress
✅HER2 IHC
✅prior chemo
✅age
✅base CNS mets
✅anthracycline use

11/22 #TumorBoardTuesday #BreastCancer #SABCS22
👩🏻‍🏫Mini tweetorial 9

🧐Does T-DXd work in all subgroups?

✅Safety profile consistent among subgroups
✅No differences in overall incidence of ILD observed

12/22 #TumorBoardTuesday #BreastCancer

✨Destiny-Breast 04✨
T-DXd AEs

Most common:
🦴neutropenia/leukopenia
🩸anemia
🩸thrombocytopenia
🤢nausea
🤮Vomiting
🚽Diarrhea
🚽Constipation
😴fatigue
⬆️AST
🧑🏼‍🦲Alopecia
⬇️🍽️Decreased appetite

🚨Significant AE is ILD/pneumonitis🚨

13/22 #TumorBoardTuesday #BreastCancer

✨Destiny-Breast 04✨

🫁ILD with T-DXd

12% incidence in DB-04

📍Symptom awareness
📍prompt work-up critical‼️

Common symptoms:
😮‍💨Dyspnea
😷Cough
🥱Malaise
🫁Chest pain
🥶Hypoxemia
🤒Fever

📚 sciencedirect.com/science/articl…

14/22 #TumorBoardTuesday
🫁ILD with T-DXd

⚡️patient + provider ed important⚡️

👀Proactive patient monitoring
🕵🏻‍♀️symptom monitoring
🩻regular CT assessments (q9-12wk)
🗓️Initiate w/u early
💊Treatment includes 👺steroids prn, ⏸️ pause T-DXd (D/c grade≥2) & involve multi-d team!!

15/22 #TumorBoardTuesday
Back to our case🔎

Progress of disease in liver & pleura
2022: 🔀 switched to trastuzumab deruxtecan

🩻Improving disease on the scans🎉

🤔If disease progression or toxicity develops, what would you try next?

16/22 #TumorBoardTuesday
🔥Bonus🔥Mini tweetorial
✨TROPICS-02✨

🔹Global, multi center, open-label
🔸phase III
🔹randomized 543 pts to sacituzumab govitecan (10 mg/kg days 1 & 8 every 21 days) vs physicians’ choice of chemo (eribulin, cap, gem, or vinorelbine)

17/22 #TumorBoardTuesday
🔥Bonus🔥Mini tweetorial
✨TROPICS-02✨

🔸Patients received 2-4 prior lines of tx (avg 3), incl endocrine therapy & inhibitors of cyclin D kinases 4 & 6 (CDK4/6)
🎉Newly approved for HR+/HER2- or low locally advanced or MBC (already approved for TNBC)

18/22 #TumorBoardTuesday #BreastCancer
🔥Bonus🔥Mini tweetorial
✨TROPICS-02✨

🔹Pts randomized to to receive sacituzumab govitecan (n=272) vs TPC (n=271)

📚@hoperugo @dradityabardia @JavierCortesMD @evaciruelos @jhaveri_komal @stolaney1
ascopubs.org/doi/abs/10.120…

19/22 #TumorBoardTuesday #BreastCancer
🔥Bonus🔥Mini tweetorial
✨TROPICS-02✨

📌 Results
🎉OS 14.4 mo vs 11.2 mo (HR 0.79)

📍subgroup analysis from #ESMO22 shows improvement in PFS similar in HER2-low and HER2 IHC 0 subgroups

👍🏽Great option for HER2 low disease

20/22 #TumorBoardTuesday #BreastCancer
🔥Bonus🔥Mini tweetorial
✨TROPICS-02✨

📌Saci AEs
Abdominal pain
🤢nausea
🤮Vomiting
🚽Diarrhea
🚽Constipation
😴fatigue
🦴Neutropenia
🩸Anemia
🧑🏼‍🦲Alopecia
⬇️🍽️Decreased appetite

21/22 #TumorBoardTuesday #BCSM
Other HER2-low trials

Ongoing:
✨DB-06✨
T-DXd vs TPC (Cape, Paclitaxel, Nab-Paclitaxel)
🔹patients with HER2-low MBC with progression on endo tx
🔸No prior chemo allowed

✍️ clinicaltrials.gov/ct2/show/NCT04…

22/22 #TumorBoardTuesday #BreastCancer
Other HER2-low trials

Ongoing:
✨DB-08✨
T-DXd with different drug combos in HER2-low MBC
Durvalumab
Paclitaxel
Capivasertib
Anastrozole
Fulvestrant
Capecitabine

✍️ clinicaltrials.gov/ct2/show/NCT04…

#PostTest Q1️⃣ #TumorBoardTuesday
👉🏽#CME Eval🔗 integrityce.com/tbtEval

🤔@drteplinsky taught us progress of HER2+ low #breastcancer
🤨What would U pick for 60y👩🏻
ER+/PR-/HER2-low mBC
recent dz prog➡️liver & pleura after 5mo paclitaxel (prev tx AI+CDK4/6i, fulv, ever+exem,&cap)

#PostTest Q2️⃣ #TumorBoardTuesday
👉🏽 Free CME (AMA & MOC)
🔗 integrityce.com/tbt

🤔What subsequent tx would you select for 👆🏽this 60yo 👩🏻 woman with ER+/PR-/HER2-low mBC if she experienced disease progression while receiving trastuzumab deruxtecan?