Thread by @shilpaonc

1/ #OncTwitter #NephTwitter
✅#RenalCell #TumorBoardTuesday #MedTweetorial 🧵
w @brian_rini @shilpaonc @katy_beckermann

🦺TKI/IO safety data
🥽Tox to look 4
⛑AE mgmt

🆓#CME @BonumCe🔗bit.ly/3VDaK81
Support by edu grants from Eisai & @Merck

🟢What's your specialty?

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🆓#CME info ➕ full ref list🗒️ 👉 bit.ly/3VDaK81

✳️The critical elements👇

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🟢 Which of the following TKI/IO combo regimens is 🚫NOT approved by the FDA for the frontline mgmt of #RenalCell carcinoma?

4/ #TumorBoardTuesday #BonumCE #OncTwitter #RenalCell

💎Combo txs as SOC for 1st line mRCC

TKI/ICI combos:
🔸lenvatinib (TKI) + pembrolizumab (PD-1 mAb)
🔸axitinib (TKI) + pembro
🔸cabozantinib (TKI) + nivolumab (PD-1 mAb)

Dual ICI combo:
🔸ipilimumab (CTLA-4) + nivo

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🔑Ph3 trls #KEYNOTE426, #CLEAR, #CheckMate9ER, #CheckMate214

💎Each combo regimen ⬆️PFS, OS, & ORR vs sunitinib
💎Axi-avelumab approved but OS data immature
💎Benefit across IMDC risk groups
💎Axi-pembro=longest f/u among approved TKI-ICI in RCC

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✳️Dual ICI combo (ipi + nivo) also approved tx option

💎#CheckMate214 - ipi + nivo vs sunitinib
✅Longest follow-up in frontline RCC (>5 years)
✅OS and PFS favor combo tx in int/poor risk pts

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🟢 Which of the following is a characteristic feature of the most common toxicities associated with anti-angiogenic therapies?

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Combo tx =possible⬆️tox➡️can lead to tmt🛑

✨Anti-angio inhibitors=multi🎯TKIs
✨AEs related to shared 🎯s (e.g. VEGFR)=predictable class tox
✨Some nuance due 2 diff🎯/potency
✨Typ occur 1st few wks of ▶️ tx
✨Broadly dose-dependent

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ICI AEs related to immunostimulatory MOA (irAEs)
✳️Most mild/mod severity & reversible
⚠️CAN become sev/fatal if not promptly Dx & Tx⚠️
👉Impact virtually any bodily system
🗓️Most occur “early” (<14wks after start tx), some can occur mos/yrs later

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🟢 Which of the following is an AE that is commonly observed with both ICIs and TKIs?

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Some AEs attributable to either drug
These 🔂overlapping tox can complicate pt mgmt

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🔬Common tox in pivotal Phase 3 trials of TKI-ICI combos🔬
#KEYNOTE426 #CLEAR #CHECKMATE9ER #JAVELINrenal101
🔹Diarrhea
🔸HTN
🔹Hypothyroidism
🔸Fatigue
🔹PPES
🔸Loss of appetite

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🔬Common tox in pivotal P3 #CHECKMATE214 trial of dual ICI combo🔬
🔸Fatigue
🔹Pruritus
🔸Diarrhea
🔹Rash
🔸Nausea

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Effective tox mgmt ➡️optimize pt outcomes✅

🩺 Mgmt strategies include...🩺
🔹Prevention
🔸Monitor BP, urine protein, thyroid & liver function
🔹Dose modification (⏸️⬇️🛑)
🔸Supportive care

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🟢Pt w mRCC
🔸Initiated tx w pembro + lenva
🔹Developed G3 diarrhea
🔸Lenva withheld & anti-diarrheal treatment initiated 🔹Diarrhea now resolved.

🟢What next step is best for the pt?

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If tox occurs,🔑strategy
🔸⬇️dose TKI
🔹Dose flex of TKIs>ICIs
🔸Axi fastest washout (hrs)

🔹Lenva 14mg➡️10mg ➡️8mg
🔸Axi 5mg➡️3mg➡️2mg
🔹Cabo 40mg QD➡️20mg QD➡️20mg QOD

Many pts need dose⬇️
BUT most can stay on tx if manage pt expectations

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🔬Research needed to ⬇️ tox while maintaining efficacy

❓Alternative dosing strategies (incl. dose breaks)
❓Effects of dose ⬇️ on pt outcomes
❓Effects of reduced ▶️ dose on pt outcomes

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❓Effects of reduced ▶️ dose on pt outcomes

Limited prospective trial data to date: lenva 14mg ▶️ dose

🔸Lenva 14mg vs 18mg + pembro in EC ➡️14mg ▶️dose ⬇️AEs & maint efficacy

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Plethora of options…❓Which combo to pick❓
Lack H2H trials or reliable biomarkers∴choice based on clin features & other factors, including:

🔸Tumor burden
🔹Comorbidities
🔸Pt age/func status
🔹Physician/pt pref
🔸QoL

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💡Examples for trtmnt selection:
⛏️High tumor burden➡️ ICI/TKI ➡️short⏱to response/deep responses

⛏️Older/frail pt➡️ axi-pembro ➡️greatest flexibility in dosing to avoid AEs

⛏️Uncontrolled HTN/CHF➡️ ipi-nivo ➡️TKIs contraindicated

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🔮Is triplet tx the future?
#COSMIC313=nivo + ipi + cabo int/poor-risk #RenalCell

3x tx sig⬆️PFS vs pbo+nivo+ipi (mPFS: NR vs 11.3mos)
🚫⬆️OS - follow-up ongoing
Sig ⬆️in tox - G3/4 TRAEs in 73% pts vs 41% for pbo arm
TRAEs leading to tx🛑: 12% vs 5%

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🔑Points
🔸TKI/ICI combos SOC 1L met #RenalCell
🔹⬆️PFS, OS & ORRs vs sunitinib all risk groups
🔸⬆️risk tox & potential 4 o’lap tox complicates pt mgmt
🔹Addl options incl axi-ave, dual ICI combo, & TKI monotx
🔸Choice guided by pt- & diz-specific factors

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Thanks for joining me & @TumorBoardTuesday

🔴Answer post-polls👇
Claim🆓#CME 👉bit.ly/3VDaK81

🔴Post Poll 1️⃣
🔴Which of the following TKI/IO combo regimens is 🚫NOT approved by the FDA for the frontline mgmt of #RenalCell carcinoma?

24/#TumorBoardTuesday #BonumCE #RenalCell
#OncTwitter #NephTwitter #MedTwitter
#CME➡️ bit.ly/3W0R1Pq

🔴Post Poll 2️⃣
🔴Which of the following is a characteristic feature of the most common toxicities associated with anti-angiogenic therapies?

25/#TumorBoardTuesday #BonumCE #RenalCell
#OncTwitter #NephTwitter #MedTwitter

🔴Post Poll 3️⃣
CME➡️ bit.ly/3W0R1Pq

🔴Which of the following is an AE that is commonly observed with both ICIs and TKIs?

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🔴 Post Poll 4️⃣
#CME➡️ bit.ly/3W0R1Pq

Pt w mRCC
🔸Initiated tx w pembro + lenva
🔹Developed G3 diarrhea
🔸Lenva withheld & anti-diarrheal treatment initiated 🔹Diarrhea now resolved.

🔴What next step is best for the pt?

27/#TumorBoardTuesday #BonumCE
#OncTwitter #NephTwitter #MedTwitter

🧗Climb your next mountain ⛰️
🔥#RenalCell Carcinoma Fireside Chat🎥🔥
🗓 Thur, Dec 15 @ 8pm ET / 5pm PT
w/ experts @brian_rini @shilpaonc @katy_beckermann