@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)
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