Thread by @n8pennell

@TumorBoardTues 1/17 #TumorBoardTuesday #LCSM #OncTwitter
50y 👩🏻 never 🚬 presents with cough

🩻CT: 2cm RLL 🫁 mass & pleural effusion
💧Tap of pleural fluid: adenocarcinoma TTF1+ (T1bN0M1a) Stage 4A #NSCLC
🧪NGS: exon19 deletion EGFR mutation & PDL1 70%+

🤨What’s most appropriate initial tx?

@TumorBoardTues 2/17 #TumorBoardTuesday #LCSM

👩🏻 starts osimertinib with resolution of effusion

She has🧴dry skin & occasional 💩diarrhea managed with loperamide

After 18 months she develops headache
🧲MRI brain shows new 2cm 🧠 metastasis with edema

🤨What’s the most appropriate next step?

@TumorBoardTues 3/17 #TumorBoardTuesday #LCSM
👨🏼‍🏫Mini tweetorial 1

EGFR mutations

📍≈15% of🫁adenocarcinomas
📍More common in light or never smokers, women, & Asian ethnicity
📍90% sensitizing & either exon19 del/ins or L858R mut in exon21
@NatureRevCancer Sharma et al
nature.com/articles/nrc20…

@TumorBoardTues @NatureRevCancer 4/17 #TumorBoardTuesday
👨🏼‍🏫Mini tweetorial 2
Many trials (ex IPASS) show EGFR TKIs >> chemo

‼️Testing each adenoca pt for EGFRm is critical‼️

CAP/IASLC rec test ALL regardless of demo or🚬hx
📚@tonymok9 @NEJM bit.ly/3UWzSqv
📚Lindeman @JTOonline bit.ly/3fr7zjB

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline 5/17 #TumorBoardTuesday #LCSM
👨🏼‍🏫Mini tweetorial 3

3rd gen EGFR TKI osimertinib >> older TKIs in ph 3 FLAURA trial

👍🏽@FDA approved in 2018 for 1L EGFRm+ #NSCLC
🔹ORR 80% & dur of response 17 months
med OS 34.5 months
📚@ramalingamMD @NEJM bit.ly/3dW458F

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD 6/17 #TumorBoardTuesday #LCSM
👨🏼‍🏫Mini tweetorial 4

⚠️Limited (oligo) progression, locally ablative tx (LAT) can delay change of treatment by avg of 6 months

📚@JackWestMD @HosseinBorghaei bit.ly/3EeNtDO

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei 7/17 #TumorBoardTuesday #LCSM
👨🏼‍🏫Mini tweetorial 5

🛑Don’t be tempted to use pembro with ⬆️ PDL1!

📍Pembro trial in 1L EGFRm+ pts had 0% ORR in first 10 pts
📚bit.ly/3rr7gYQ

⚠️Combo of osi + anti-PD(L)1 assoc with ⬆️ rate of 🫁 pneumonitis⚠️

📚bit.ly/3rrHCDo

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei 8/17 #TumorBoardTuesday

✨HERTHENA-Lung 1 trial✨

🔹HER3 antibody-drug conjugate (ADC) patritumab deruxtecan (DXd) tested in EGFRm+ pts post-osi
🔹ORR: 39%
🔹median PFS 8.2 m
💥no relationship to HER3 expression💥

📚bit.ly/3fDKdaL

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei 9/17 #TumorBoardTuesday #ASCO21 #NSCLC

✨Confirmatory HERTHENA-Lung 2 vs SOC chemo is ongoing✨

🧑‍🔬NCT05338970 clinicaltrials.gov/ct2/show/NCT05…

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei 10/17 #TumorBoardTuesday #LCSM

Another good option:

🥔Datopotamab-DXd

✨TROP2✨

🎯drug has been tested in previously treated pts with EGFRm+ #NSCLC, with ORR 35% & DOR 9.5 months

📚 @Annals_Oncology bit.ly/3UQfgjA

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology 11/17 #TumorBoardTuesday #LCSM

✨Now testing #NSCLC pts & without actionable alterations (TROPION-Lung01-02) ✨

📚 Mol Cancer Ther bit.ly/3M3LG6d

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology 12/17 #TumorBoardTuesday #LCSM
Amivantamab and lazertinib

⚡️Don’t forget amivantamab (MET-EGFR bispecific) & lazertinib (3rd gen EGFR TKI)⚡️

📍Chrysalis-2 study had ORR of 25-30% in previously treated EGFRm+ #NSCLC patients!
📚bit.ly/3yd3Lce

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology 13/17 #TumorBoardTuesday #LCSM
Emerging next-gen TKIs

🧑‍🔬Many being tested but🤷🏼‍♂️no real clinical data yet

Some (not full list!) examples:
🔹JIN-A02
🔹BBT-176
🔹BLU-945

‼️Enrollment to clinical trial should be optimal choice for any refractory #NSCLC pt‼️
cancer.gov/about-cancer/t…

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology 14/17 #TumorBoardTuesday
Back to our case🔎

👩🏻 undergoes SRS to the 🧠 lesion & cont osi

📅 6 months later develops new liver lesions & worsening effusion
🔬Rebiopsy confirms adenocarcinoma with original EGFR mutation only

Now what?

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology 15/17 #TumorBoardTuesday
Importance of new biopsy at PD to rule out #SCLC & new 🎯

🤨Should you rebiopsy patients with EGFRm+ #NSCLC at time of emerging resistance?
👍🏽YES!

📌Remember to rule out SMALL CELL transformation which occurs in ≈8%
📚Ham et al bit.ly/3C5zs8t

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology 16/17 #TumorBoardTuesday #LCSM
Toxicity of patritumab DXd

📌AE’s to remember for patritumab DXd

Most toxicity related to chemo payload:
🩸cytopenias
💩GI tox
🫁≈ 5% rate of interstitial lung disease (ILD)

🕵🏼‍♂️watch for pulm toxicity
📚bit.ly/3fDKdaL

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology 17/17 #TumorBoardTuesday #LCSM
Case update

👩🏻 good response to patritumab-DXd for 8 months 🙌🏽

No significant toxicity, but glad that there are multiple options at time of progression!

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology #PostTest Q1️⃣ #TumorBoardTuesday
👉🏽CME Eval 🔗 integrityce.com/tbtEval

🤔@n8pennell taught us about 3L #NSCLC, test your 🧠 with 2 quick❓

🧐What 1st tx would you pick for:
50yo👩🏻
🚭
🫁mNSCLC (T1bN0M1a, adenoca, TTF1+)
🧬EGFRdel19 & 70%+ PD-L1 by NGS

@TumorBoardTues @NatureRevCancer @TonyMok9 @NEJM @JTOonline @FDA @RamalingamMD @JackWestMD @HosseinBorghaei @Annals_Oncology #PostTest Q2️⃣ #TumorBoardTuesday
👉🏽Free CME🔗: integrityce.com/tbt

🧐What subsequent tx would you pick for:
50yo👩🏻
🚭
mNSCLC (adenoca, EGFRdel19, PD-L1 70%+)
new liver lesions
🫁worsening effusion 6 mos after SRS to 🧠 lesions
continued osimertinib

(Assume all tx avail)