Thread by @JohnEbbenMDPhD

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD 1/8 #TumorBoardTuesday
🔬🧬@CharuAggrawalMD @ADesaiMD taught us about EGFR mutations in #LungCancer–specifically, new 2L strategies for EGFRexon20m.

➡️Here's this week's Thursday Case🎀
Pick up your 🆓#CME
ALL CME 🔗: integrityce.com/tbt
CME eval🔗: integrityce.com/tbteval

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD 2/8 #TumorBoardTuesday
Thurs Case🎀

Take🏠messages:
We discussed #EGFR mutations in #LungCancer
✅Not all EGFR mutations are the same!
✅Osimertinib=tx for most activating EGFR mutations
✅…but exon20insmut more resistant to TKIs
✅Amivantamab, mobocertinib= 2L strategies

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD 2.5 / 8 #TumorBoardTuesday

📚We captured as much of @CharuAggrawalMD @ADesaiMD’s discussion as we could in this moment: twitter.com/i/events/15463…

CRITICAL point: if you don’t look, you won’t know! RNA based NGS recommended for 🫁cancer cases to identify actionable mut

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD 3/8 #TumorBoardTuesday
Thursday Case🎀

@CharuAggrawalMD @ADesaiMD presented a case of a 63yo 👨🏽 (never smoker) with stage IVA 🫁#NSCLC & ECOG PS= 0.

Key question that we have seen over and over again- what next? Do we wait for more testing, or start tx?

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD 4/8 #TumorBoardTuesday
Thursday Case🎀

Targeted tx for actionable mut is standard-of-care; getting the sequence wrong (starting IO first) can lead to more tox for pt over long term.

Why is NGS so important? MANY pts have targetable muts. This has contributed to ⬆️ survival!

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD 4.5/8 #TumorBoardTuesday
Thursday Case🎀

So…we waited for NGS—and found an EGFR ex20 insertion mutation!

🤔What to do now❓ Not the most common EGFR mut.
In fact, EGFRex20m= 5-12% of EGFRm

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd 5/8 #TumorBoardTuesday
Thurs Case🎀
What do we know about EGFRm?

Differential sensitivity to TKIs
☑️EGFR L858R= osimertinib
☑️Ex20= less sensitive
☑️Ex20insertions= generally NOT sens to TKI

@APessaroMD points this out: jto.org/article/S1556-….
H/T @RenoHemoOnc!

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn 6/8 #TumorBoardTuesday
Thursday Case🎀

Why are ex20 insertions so hard to tx? ATP binding pocket is smaller- most TKIs don’t fit. The ones that can (mobocertinib) may have ⬆️activity against wildtype #EGFR as well.

Ex20 insertions= more common in 🫁adeno, women, and 🚭

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc 7/8 #TumorBoardTuesday
Thursday Case🎀

So how do we treat ex20 insertion?

✅1L= standard chemo (cis/pem+bev)
✅2L= Amivanatmab or mobocertinib
🔹AMI= mAb targeting EGFR & MET
🔹Mobocertinib= next gen TKI

BUT trials ongoing, testing chemo+inhib in 1L

https://twitter.com/CharuAggarwalMD/status/1547015916537450498?s=20&t=wqBZO9Sz5Jrk5OkOokfRXQ

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc 7.5/8 #TumorBoardTuesday
Thurs Case🎀

Choosing a 2L tx:
🧠mets- more likely to see activity w mobocertinib
🤢Specific tox- infusion rxn to ami, ❓from polysorbate 80 formulation.

S/o to allergists who offer de-sensitization to help us tx pts! @JenniferLiMD @MGHAllergy

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc @JenniferLiMD @MGHAllergy 8/8 #TumorBoardTuesday
Thurs Case🎀

🙏 Pt w prog dz on 1L chemo➡️ami; after 6 mo, progression
🤔 Trials underway w ami+ chemo, ami+ CNS penetrant TKI; many new 💊coming soon!

➡️Please be sure to join us on 7/19 when @PTarantinoMD @CaterinaSpo teach us about tx in #BRCA in #mBC

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc @JenniferLiMD @MGHAllergy @CaterinaSpo Remember #TumorBoardTuesday continues to offer AMA & now MOC credit for FREE! Don’t forget to answer the polls👇🏽
Then click this link to quickly request your credit!
CME eval🔗: integrityce.com/tbteval
ALL CME 🔗: integrityce.com/tbt

https://twitter.com/tumorboardtues/status/1547033129998815235?s=21&t=pdIntlreRIfOIy6HzbPBOw

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc @JenniferLiMD @MGHAllergy @CaterinaSpo @anguspratt @EricaMarieRomn1 @KRASKickers @AndresFCardonaZ @thenasheffect @ALKpositiveINT @EgidiusLambrech @JenniferLiMD @EugeneManley @manjuggm @Ipreeshagul @JoelNealMD @HWakeleeMD @glopesMD @jmsuga @jacobadashek @IbiayiMD @CBelaniMD @ApassaroMD @DasMillie11 @manalipatelmd

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc @JenniferLiMD @MGHAllergy @CaterinaSpo @anguspratt @EricaMarieRomn1 @KRASKickers @AndresFCardonaZ @jillfeldman4 @JackWestMD @Drrtee @CatherineShuMD @VivekSubbiah @nlinmd @OncBrothers @filimasini @ksivaprasadk @DivyaGuptaMD @visheshkhanna @letswinpc @LungAssociation @LungCancerDr @Tony_Calles @BairdAM @mlazqui @DSudhanPhD @EloySantosPujol @n8pennell @DrBonillaOnc @alexdrilon

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc @JenniferLiMD @MGHAllergy @CaterinaSpo @anguspratt @EricaMarieRomn1 @KRASKickers @AndresFCardonaZ @drRTee @CatherineShuMD @VivekSubbiah @nlinmd @OncBrothers @filimasini @DevikaDasMD @LealTiciana @deeptibehl1 @FawziAbuRous @AnaVManana @esinghimd @StephenVLiu @christine_lovly @HosseinBorghaei @DrSteveMartin @NarjustFlorezMD @LeciaSequist @Latinamd @EleanorKMishra @DrBalukuJoseph @brucekirenga

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc @JenniferLiMD @MGHAllergy @CaterinaSpo @anguspratt @EricaMarieRomn1 @KRASKickers @AndresFCardonaZ @drRTee @CatherineShuMD @VivekSubbiah @nlinmd @OncBrothers @filimasini @DevikaDasMD @deeptibehl1 @FawziAbuRous @AnaVManana @esinghimd @StephenVLiu @christine_lovly @FredrikThege @cwilliamszf @LeQuesneLab @OqKenzaMD_path @drtclay @DrAnnaMcGuire @PatrickCMa1 @Aiims1742 @melisawongmd

@TumorBoardTues @CharuAggarwalMD @ADesaiMD @Latinamd @PTarantinoMD @LealTiciana @NarjustFlorezMD @ALKpositiveINT @EGFRResisters @DFEGFRcenter @APassaroMD @JackWestMD @jillfeldman4 @HwakeleeMD @manalipatelmd @EgfrUk @NSethakorn @DrSteveMartin @lcrf_org @LCleaders @DrBonillaOnc @JenniferLiMD @MGHAllergy @CaterinaSpo @anguspratt @EricaMarieRomn1 @KRASKickers @AndresFCardonaZ @drRTee @CatherineShuMD @VivekSubbiah @nlinmd @OncBrothers @filimasini @DevikaDasMD @deeptibehl1 @FawziAbuRous @AnaVManana @esinghimd @StephenVLiu @christine_lovly @FredrikThege @cwilliamszf @LeQuesneLab @OqKenzaMD_path @drtclay @DrAnnaMcGuire @PatrickCMa1 @Aiims1742 BONUS! @ADesaiMD prepared an awesome graphic that summarizes the tweetorial and major points around mgmt of exon20ins in #EGFR-driven #NSCLC.