Thread by @TumorBoardTues

1/#OncTwitter #TumorBoardTuesday #MedTweetorial 🧵

✅#EndometrialCancer AE deep dive🤿
🧪Trial results
🔬Tox for TKI-ICI
w @DrMMurphy @MeganLeigh127 & us!

🆓#CME @BonumCe🔗bit.ly/3VBGJEJ
Supported by edu grants from Eisai & @Merck

🟢What's your specialty?

2/#TumorBoardTuesday #BonumCE #OncTwitter #gyncsm #gynonc #EndometrialCancer #MedTweetorial

🆓 CME > full info➕ref list🗒️& program archive
👉bit.ly/3VBGJEJ

🔑#CME info👇

3/#TumorBoardTuesday #BonumCE #OncTwitter #GynOnc #gyncsm #EndometrialCancer

🟢Which I/O +🎯tx combo is FDA approved for treatment of advanced or metastatic #EndometrialCarcinoma?

nivo = nivolumab
dostarlimab = dostarlimab-gxly
pembro = pembrolizumab

4/#TumorBoardTuesday #BonumCE #OncTwitter #gyncsm #gynonc #EndometrialCancer

If you picked pembro + lenva…
You’re right🎉

Pembro (PD-1🎯mAb) + lenva (multi-🎯TKI)
➡️🏁accelerated approval adv EC in 2019

Ph3 confirmatory trial✅➡️#KEYNOTE-775
➡️full FDA approval 2021

5/#TumorBoardTuesday #OncTwitter #GynCSM #gynonc

#EndometrialCancer most common gyn cancer in🇺🇸

Rates 📈
Est in 2022…
📊New cases: 69,950
📊Deaths: 12,550

Most pts dx early stage - gd prognosis✅

Approx 9% dx met disease➡️5y survival <20%➡️plat chemo SOC 1st line tx

6/#TumorBoardTuesday #BonumCE #OncTwitter #gyncsm #gynonc

After progression on chemotx, tx for metastatic #EndometrialCancer is influenced by tumor molecular subtype

🧬Cancer Genome Atlas ID’d 4️⃣ mol subclasses…
1️⃣POLE ultramutated
2️⃣dMMR/MSI-H
3️⃣Copy # low
4️⃣Copy # high

7/#TumorBoardTuesday #BonumCE #OncTwitter #gyncsm #gynonc

🧬Faulty DNA repair (dMMR/MSI-H)➡️high tumor mutation burden
➡️more tumor neoantigens
➡️sensitivity to ICI

💎Two FDA approved ICIs in dMMR/MSI-H #EndometrialCancer:
🔹Pembro (PD-1 mAb)
🔹Dostarlimab (PD-1 mAb)

8/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc #EndometrialCancer

Pivotal trials leading to FDA approval in 2L met MSI-H/dMMR #EndometrialCarcinoma

🔸Pembro: #KEYNOTE158 (phase 2)
🔹Dostarlimab: #GARNET (phase 1)

🔑Efficacy & safety data 📷👇

9/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc #EndometrialCancer

⚙️Lenva=multi🎯TKI (incl VEGFR)
🛑Blocks angiogenic signaling
VEGFR signals also have immunosuppressive role

⚙️Pembro=ICI
💪Boosts anti-tumor immune response

🔑Combo tx=synergistic anti-tumor activity

10/#TumorBoardTuesday #GynCSM

Tx for adv MSS or pMMR #EndometrialCancer tumors was🔑unmet need until lenva-pembro approval

Pivotal P3 #KEYNOTE775 trial confirmed✅OS, PFS, & ORR benefit vs chemo for adv/met EC

⭐Benefit independent of dMMR/MSI status
🆕Update @ #ESMO2022

11/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc

🟢What is the most common grade 3 or higher toxicity associated w/ the combination of pembro & lenva in pts w/ #EndometrialCancer?

12/#TumorBoardTuesday #GynCSM #gynonc #EndometrialCancer

✏️Lenva-pembro tox distinct from chemotx
✏️Safety profile of combo tx consistent w those of individual agents
✏️Most common any grade & grade 3+TRAE = HTN
✏️Shortest⏱to onset: HTN
✏️Later: hypothyroidism & weight loss⬇️

13/#OncTwitter #TumorBoardTuesday

🔑s to tackling lenva-pembro tox:

📝Comprehensive mgmt plan
🏫Pt/caregiver education
⚠️Regular monitoring during tx (BP, thyroid & liver function, urine protein)
👩‍⚕️MDTeam care
⚡Watch out for comorbidities
💊Supportive care
💊TKI dose mods

14/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc #EndometrialCancer

🚨VEGFR TKI-related class tox e.g. HTN, proteinuria
🗓Typ occur 1st few wks tx
💊Dose-dependent
🧮Managed w dose mods & supportive care (e.g. anti-hypertensive)

15/#TumorBoardTuesday #BonumCE #OncTwitter #gyncsm #gynonc #EndometrialCancer

🟢During tx w/ pembro-lenva, a pt develops grade 3 HTN requiring reduction in lenva. Starting dose of lenva was 20mg.

Which dose is recommended for lenva now?

16/#TumorBoardTuesday #BonumCE #OncTwitter #gyncsm #gynonc #EndometrialCancer

💊 Lenva dose mods = dose reduce⬇️or withhold🛑for more severe tox

Recommended lenva starting ▶️dose adv EC: 20mg QD
🥇1st dose⬇️14mg
🥈2nd dose⬇️10mg
🥉3rd dose⬇️8mg

17/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc #EndometrialCancer

45.6% pts ≥2 ⬇️lenva dose#KEYNOTE775
🔸Often need new 30d dose pack b4 finishing current supply

🆕Eisai dose exchange program - cover all indicated dose⬇️🔗bit.ly/3gYHvOd

18/#TumorBoardTuesday #EndometrialCancer

🤔Pre-empt tox w reduced lenva starting▶️dose?

Retro analysis 70 pts: 20mg vs lower dose (mostly 14mg)
📈# dose reductions &📉 time to tox @ 20mg
ORR, PFS, & OS did NOT differ significantly w lower dose

✳️Need prospective data✳️

19/#TumorBoardTuesday #GynCSM #EndometrialCancer

🚨Pembro-related immune tox🚨
🔸Can affect any organ @ any time during/after tx
🔹Can become severe/fatal if not promptly dx & tx
🔸Typically reversible (excl. endocrine)
🔹Managed w immunosuppressive tx - mainly corticosteroids

20/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc #EndometrialCancer

🟢During treatment w pembro & lenva, pt develops frequent, loose, watery stools

How could you quickly determine which drug is causing the diarrhea?

21/#TumorBoardTuesday #GynCSM

Overlapping tox: some AEs attributable to either drug
✅Need to ID etiology to choose correct mgmt strategy
⏱TKI ½-life allows rapid drug washout➡️w/hold lenva + see if tox resolves
Common overlapping tox: diarrhea, fatigue, rash, hypothyroidism

22/#TumorBoardTuesday

🔑Points
🔸Lenva-pembro=impt tx option 4 adv/met EC w MSS or pMMR
🔹⬆️OS, PFS, & ORR vs chemotx
🔸Distinct tox profile vs chemotx
🔹Most common tox=lenva-associated HTN
🔸Potential 4 o’lapping tox complicates mgmt
🔹Mgmt: lenva dose mod & steroids 4 irAEs

23/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc

Thanks for joining!
👋Claim🆓#CME👉bit.ly/3jCyVFJ
🛑Before you leave…answer polls👇

🔴Post Poll1️⃣
🔴Which I/O +🎯tx combo is FDA approved for treatment of advanced or metastatic #EndometrialCarcinoma?

24/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc

🏆#CME➡️ bit.ly/3jCyVFJ

🔴Post Poll2️⃣
🔴What is the most common grade 3 or higher toxicity associated w the combo of pembro & lenva in pts w #EndometrialCancer?

25/ #TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc

#CME➡️bit.ly/3jCyVFJ 🏆

🔴Post Poll 3️⃣
🔴During tx w/ pembro-lenva, a pt develops grade 3 HTN requiring reduction in lenva. Starting dose of lenva was 20mg.

Which dose is recommended for lenva now?

26/#TumorBoardTuesday #BonumCE #OncTwitter #GynCSM #gynonc

🏆#CME➡️bit.ly/3jCyVFJ

🔴 Post Poll 4️⃣
🔴During treatment w pembro & lenva, pt develops frequent, loose, watery stools. How could you quickly determine which drug is causing the diarrhea?

27/

🏔Conquer your next #EndometrialCancer🏔
📍Here @TumorBoardTues
🔥EC Fireside Chat🎥🔥
🗓Thur, Jan 19 @ 8pm ET / 5pm PT