@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DAielloMD @DrRiyazShah @DrSanjayPopat @TomVargheseJr @acmoorephd @McPerego @IntegrityCE @JanssenUS @AstraZeneca 1/22 #TumorBoardTuesday #LungCancer #OncTwitter
57y π©π½ short of breath
PMH: GERD
π¬3pk/yr smoking hx, quit 25yrs prior
π©»CT: bilat π« nodules
π¬bx: adenocarcinoma, PDL1 85%
π§²MRI brain: 5 mets, each < 3mm
Asymptomatic
Stage IV NSCLC adenocarcinoma
π¬Liquid bx: EGFR L858R
Next?
57y π©π½ short of breath
PMH: GERD
π¬3pk/yr smoking hx, quit 25yrs prior
π©»CT: bilat π« nodules
π¬bx: adenocarcinoma, PDL1 85%
π§²MRI brain: 5 mets, each < 3mm
Asymptomatic
Stage IV NSCLC adenocarcinoma
π¬Liquid bx: EGFR L858R
Next?
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DAielloMD @DrRiyazShah @DrSanjayPopat @TomVargheseJr @acmoorephd @McPerego @IntegrityCE @JanssenUS @AstraZeneca 2/22 #TumorBoardTuesday #LCSM @MMarmarelis @MPishvaian @JohnEbbenMDPhD @cbcbc1971 @LatinaMD @RamalingamMD @SamuelKareffMD @livinglife82 #LungCancer
π©π½ π€π©π»ββοΈ#SharedDecision
π’ Start osimertinib
ποΈ 3 week visit to check on toxicities of therapy
π§Which is FALSE about osimertinib
π©π½ π€π©π»ββοΈ#SharedDecision
π’ Start osimertinib
ποΈ 3 week visit to check on toxicities of therapy
π§Which is FALSE about osimertinib
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DAielloMD @NarjustFlorezMD @LeciaSequist @LauraJBook @PatelOncology @LaurenByersMD @BairdAM @DrSteveMartin @DevikaDasMD @JSabari @ADesaiMD @jillfeldman4 @DrBivas @DAielloMD @FawziAbuRous @esinghimd @ShrutiPatelMD @JineshGheeya @sands_jacob @JuliaRotow @CharuAggarwalMD @StephenVLiu
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DAielloMD @LauraJBook @PatelOncology @LaurenByersMD @BairdAM @JSabari @jillfeldman4 @DrBivas @JineshGheeya @JuliaRotow 3/22 #TumorBoardTuesday #LCSM
π―Osimertinib - Anti-EGFR
βNo stopping PPI
β¨OCEAN: CNS ORR >70%
πjto.org
β¨FLAURA: 91% CNS ORR
AEs:
πΊAny Grade rash
π½diarrhea 58%
π@plummer_ruth @JhanelleGray @jsoriamd @reungwetwattana
ascopubs.org
π―Osimertinib - Anti-EGFR
βNo stopping PPI
β¨OCEAN: CNS ORR >70%
πjto.org
β¨FLAURA: 91% CNS ORR
AEs:
πΊAny Grade rash
π½diarrhea 58%
π@plummer_ruth @JhanelleGray @jsoriamd @reungwetwattana
ascopubs.org
ascopubs.org/doi/full/10.12β¦
CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced NonβSmall-Cell Lung Cancer
Purpose We report CNS efficacy of osimertinib versus standard epidermal growth factor receptor (EGFR...
jto.org/article/S1556-β¦
A Phase II Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis From NSCLC: Results for the T790M Cohort of the OCEAN Study (LOGIK1603/WJOG9116L)
Osimertinib has been reported to be effective against central nervous system (CNS) metastasis from a...
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Back to the caseπ
ποΈ 2 years on osimertinib
ππΌ Initial partial response
π« Multifocal disease growth in the lung
π€¨ Whatβs your next step?
Back to the caseπ
ποΈ 2 years on osimertinib
ππΌ Initial partial response
π« Multifocal disease growth in the lung
π€¨ Whatβs your next step?
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke @BijoyTelivala
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke 5/22 #TumorBoardTuesday
π©πΌβπ«Mini-Tweetorial 1π©π»βπ«
π¬What to biopsy?
@NCCN: tissue &/or liquid
πnccn.org
π₯Tissue gold standard
Recurrent/resistant dz:
π¬Redo tissue AND plasma
BUT
π¦liquid sometimes faster
βΌοΈMake sure enough tissueβΌοΈ
πnature.com
π©πΌβπ«Mini-Tweetorial 1π©π»βπ«
π¬What to biopsy?
@NCCN: tissue &/or liquid
πnccn.org
π₯Tissue gold standard
Recurrent/resistant dz:
π¬Redo tissue AND plasma
BUT
π¦liquid sometimes faster
βΌοΈMake sure enough tissueβΌοΈ
πnature.com
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke @NCCN 6/22 #TumorBoardTuesday
π©πΌβπ«Mini Tweetorial 2π©π»βπ«
πWhich TKI is best for EGFR mutant NSCLC?
β¨FLAURA
π1st trial comparing 2 EGFR TKIs
πPrior trials compared TKIs to chemo
π556 pts
πOsimertinib (3rd gen) vs earlier gen EGFR TKIs (gefitinib/erlotinib)
πnejm.org
π©πΌβπ«Mini Tweetorial 2π©π»βπ«
πWhich TKI is best for EGFR mutant NSCLC?
β¨FLAURA
π1st trial comparing 2 EGFR TKIs
πPrior trials compared TKIs to chemo
π556 pts
πOsimertinib (3rd gen) vs earlier gen EGFR TKIs (gefitinib/erlotinib)
πnejm.org
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke @NCCN 7/22 #TumorboardTuesday
π©πΌβπ«Mini Tweetorial 3π©π»βπ«
πOsimertinib
πΉIrreversible
πΈblocks EGFR-activating & T790M resistance mutations
β¨FLAURA: mPFS= 18.9 mos vs 10.2 mos with earlier TKIs
πΉORR similar
πΈmDOR= 17.2 mos vs 8.5 mos with earlier TKIs
πΉCNS penetration
β¬οΈserious AEs
π©πΌβπ«Mini Tweetorial 3π©π»βπ«
πOsimertinib
πΉIrreversible
πΈblocks EGFR-activating & T790M resistance mutations
β¨FLAURA: mPFS= 18.9 mos vs 10.2 mos with earlier TKIs
πΉORR similar
πΈmDOR= 17.2 mos vs 8.5 mos with earlier TKIs
πΉCNS penetration
β¬οΈserious AEs
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke @NCCN 8/22 #TumorboardTuesday #LungCancer
π©πΌβπ«Mini Tweetorial 4π©π»βπ«
πOsimertinib
ππ½resistance will occur
EGFR dependent
OR
EGFR independent:
β‘οΈHER2 amplification
β‘οΈMET amplification
β‘οΈMAPK/PI3K activation
β‘οΈNovel fusions
β‘οΈTransformation (SCLC, SCC)
πnature.com
π©πΌβπ«Mini Tweetorial 4π©π»βπ«
πOsimertinib
ππ½resistance will occur
EGFR dependent
OR
EGFR independent:
β‘οΈHER2 amplification
β‘οΈMET amplification
β‘οΈMAPK/PI3K activation
β‘οΈNovel fusions
β‘οΈTransformation (SCLC, SCC)
πnature.com
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke @NCCN 9/22 #TumorBoardTuesday
π©πΌβπ«Mini Tweetorial 5π©π»βπ«
πOsi
πresistance & losing T790M
β¨ AURA3: ctDNA/T790M mut NSCLC
πΉ~50% LOST T790M mutation at time of progress
πT790M loss
β Early resistance
β MET Amp, KRAS mut, fusions, & small cell transformation
πlink.springer.com
π©πΌβπ«Mini Tweetorial 5π©π»βπ«
πOsi
πresistance & losing T790M
β¨ AURA3: ctDNA/T790M mut NSCLC
πΉ~50% LOST T790M mutation at time of progress
πT790M loss
β Early resistance
β MET Amp, KRAS mut, fusions, & small cell transformation
πlink.springer.com
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke 10/22 #TumorBoardTuesday
π©πΌβπ«Mini Tweetorial 6
πOsi
πresistance & EGFR muts
β¨AURA3: tertiary EGFR mut in ~20%/T790M maintained
Common:
πΉC797S (Ex 20) ~10-26% resist to 2L
πΉPosition re other EGFR muts
β‘οΈCan re-try 1st + 3rd gen TKI combos
π@elisagiovan nature.com
π©πΌβπ«Mini Tweetorial 6
πOsi
πresistance & EGFR muts
β¨AURA3: tertiary EGFR mut in ~20%/T790M maintained
Common:
πΉC797S (Ex 20) ~10-26% resist to 2L
πΉPosition re other EGFR muts
β‘οΈCan re-try 1st + 3rd gen TKI combos
π@elisagiovan nature.com
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke @elisagiovan 11/22 #TumorBoardTuesday #LungCancer
π©πΌβπ«Mini Tweetorial 7π©π»βπ«
πOsimertinib
πCombo Tx: earlier gen TKIs + Osi
πΉCommon target (EGFR) method of resistance fueling a lot of drug development & trials
πclassic.clinicaltrials.gov
πclassic.clinicaltrials.gov
πnature.com
π©πΌβπ«Mini Tweetorial 7π©π»βπ«
πOsimertinib
πCombo Tx: earlier gen TKIs + Osi
πΉCommon target (EGFR) method of resistance fueling a lot of drug development & trials
πclassic.clinicaltrials.gov
πclassic.clinicaltrials.gov
πnature.com
classic.clinicaltrials.gov/ct2/show/NCT04β¦
(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC - Full Text View - ClinicalTrials.gov
(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC - Full Text View.
classic.clinicaltrials.gov/ct2/show/NCT05β¦
(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC - Full Text View - ClinicalTrials.gov
(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC - Full Text View.
nature.com/articles/s4141β¦
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AngelQinMD @SimonWambeke 12/22 #TumorBoardTuesday
π©πΌβπ«Mini Tweetorial 8
πNew tx after resistance
πAmivantamab β Bispecific Ab (EGFR, MET) β‘οΈanti-tumor effect
Initially in:
Exon 20 +, Pre-Treated
ORR ~40% #WCLC20 mDOR 11.1 mos
AEs:
πinfusion rxn
πΊrash
π paronychia
π½diarrhea
@Jbauml #ASCO21 Ami v RWD
π©πΌβπ«Mini Tweetorial 8
πNew tx after resistance
πAmivantamab β Bispecific Ab (EGFR, MET) β‘οΈanti-tumor effect
Initially in:
Exon 20 +, Pre-Treated
ORR ~40% #WCLC20 mDOR 11.1 mos
AEs:
πinfusion rxn
πΊrash
π paronychia
π½diarrhea
@Jbauml #ASCO21 Ami v RWD
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD 13/22 #TumorBoardTuesday #LungCancer
π©πΌβπ«Mini Tweetorial 9π©π»βπ«
β¨CHRYSALIS: Ami + Lazertinib (3rd gen TKI)
π§ͺNGS does NOT predict response
BUT
π§ͺMET IHC may predict!
π@AlexSpiraMDPhD @oncoOuLungCA @MNagasaka #ASCO21
π©πΌβπ«Mini Tweetorial 9π©π»βπ«
β¨CHRYSALIS: Ami + Lazertinib (3rd gen TKI)
π§ͺNGS does NOT predict response
BUT
π§ͺMET IHC may predict!
π@AlexSpiraMDPhD @oncoOuLungCA @MNagasaka #ASCO21
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 14/22 #TumorBoardTuesday #LCSM #LungCancer
π©πΌβπ«Mini Tweetorial 10π©π»βπ«
β¨CHRYSALIS 2
πOsi β‘οΈ Chemo β‘οΈ Ami + Laz
πORR 36%, median duration of response nr at 8 months
πPrelim CNS activity
πascopubs.org
π©πΌβπ«Mini Tweetorial 10π©π»βπ«
β¨CHRYSALIS 2
πOsi β‘οΈ Chemo β‘οΈ Ami + Laz
πORR 36%, median duration of response nr at 8 months
πPrelim CNS activity
πascopubs.org
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 15/22 #TumorBoardTuesday
π©πΌβπ«Mini Tweetorial 11π©π»βπ«
πNovel directions
π―HER3 targeted Abs
π«§HER3 expressed on cell surface in NSCLC (β€ 75%)
πΉPatritumab deruxtecan (HER3-Dxd): antibody-drug conjugate (ADC)
π«§Chemo (topo II inhibitor) to cells with HER3
πncbi.nlm.nih.gov
π©πΌβπ«Mini Tweetorial 11π©π»βπ«
πNovel directions
π―HER3 targeted Abs
π«§HER3 expressed on cell surface in NSCLC (β€ 75%)
πΉPatritumab deruxtecan (HER3-Dxd): antibody-drug conjugate (ADC)
π«§Chemo (topo II inhibitor) to cells with HER3
πncbi.nlm.nih.gov
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 16/22 #TumorBoardTuesday
π©πΌβπ«Mini Tweetorial 12π©π»βπ«
πHER3-Dxd
Ongoing trials
πEGFR-mutated, Osi-resistant NSCLC
Prelim Data
πRR 39% in 44 pts who received Osimertinib prior
β¨U3-1402
πclinicaltrials.gov
π€¨Response across mechanisms?
π€Active regardless of HER3 IHC express?
π©πΌβπ«Mini Tweetorial 12π©π»βπ«
πHER3-Dxd
Ongoing trials
πEGFR-mutated, Osi-resistant NSCLC
Prelim Data
πRR 39% in 44 pts who received Osimertinib prior
β¨U3-1402
πclinicaltrials.gov
π€¨Response across mechanisms?
π€Active regardless of HER3 IHC express?
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 17/22 #TumorBoardTuesday #LCSM
Back to our caseπ
π¦Liquid biopsy
π§ͺNGS did not identify resistance mechanism
π¬Tissue bx
βNo SCLC transformation
π§ͺNGS neg for resistance mechanism
πFISH pos for MET amp
π’Start osimertinib + capmatinib 200mg bid
**Note - Off label use**
Back to our caseπ
π¦Liquid biopsy
π§ͺNGS did not identify resistance mechanism
π¬Tissue bx
βNo SCLC transformation
π§ͺNGS neg for resistance mechanism
πFISH pos for MET amp
π’Start osimertinib + capmatinib 200mg bid
**Note - Off label use**
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 18/22 #TumorBoardTuesday #LCSM #LungCancer
MET resistance = MET overexpression, amp, mut, fusion
π₯Gold Standard Dx:
π¬Tissue Bx detection: FISHπ (30%) > Liq bx π¦ (15%)
MET Amp a/w poor prognosis
BUT
π―We have targeted agents now!
MET resistance = MET overexpression, amp, mut, fusion
π₯Gold Standard Dx:
π¬Tissue Bx detection: FISHπ (30%) > Liq bx π¦ (15%)
MET Amp a/w poor prognosis
BUT
π―We have targeted agents now!
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 19/22 #TumorBoardTuesday
πLevel of MET Expression
πMETi (Tepotinib) + EGFR (Gefitinib) vs plat-doublet chemo
βNo gross improvement in mPFS
BUT
β¬οΈMET IHC & MET gene amp: β¬οΈHigher ORR & mPFS, tx length
πLow accrual > trial termination
β¨INSIGHT
πncbi.nlm.nih.gov
πLevel of MET Expression
πMETi (Tepotinib) + EGFR (Gefitinib) vs plat-doublet chemo
βNo gross improvement in mPFS
BUT
β¬οΈMET IHC & MET gene amp: β¬οΈHigher ORR & mPFS, tx length
πLow accrual > trial termination
β¨INSIGHT
πncbi.nlm.nih.gov
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 20/22 #TumorBoardTuesday
Prospective Trials
β¨INSIGHT-2
πtinyurl.com
π―EGFR & MET combination
πOsi + Tepotinib (initial results)
πMET Amp
πORR > 50% at 9 mos
AEs
β¬οΈdose in ~20%
ππ½No new AE
β¨TATTON
πclassic.clinicaltrials.gov
β¨SAVANNAH
πclassic.clinicaltrials.gov
Prospective Trials
β¨INSIGHT-2
πtinyurl.com
π―EGFR & MET combination
πOsi + Tepotinib (initial results)
πMET Amp
πORR > 50% at 9 mos
AEs
β¬οΈdose in ~20%
ππ½No new AE
β¨TATTON
πclassic.clinicaltrials.gov
β¨SAVANNAH
πclassic.clinicaltrials.gov
tinyurl.com/2p8ph6zy
ESMO Congress | OncologyPRO
OncologyPRO is the home of ESMOβs educational & scientific resources, with exclusive content for ESM...
classic.clinicaltrials.gov/ct2/show/NCT02β¦
AZD9291 in Combination With Ascending Doses of Novel Therapeutics - Full Text View - ClinicalTrials.gov
AZD9291 in Combination With Ascending Doses of Novel Therapeutics - Full Text View.
classic.clinicaltrials.gov/ct2/show/NCT03β¦
Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib - Full Text View - ClinicalTrials.gov
Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib - Full Text View.
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 21/22 #TumorBoardTuesday
Back to our patient
ποΈ3 Month
π©»Scan
π«Decrease size of lung nodules
Toxicities
π©π½ Patient β¬οΈ reduces dose of MET TKI due to edema
ππΌfeels well π
Back to our patient
ποΈ3 Month
π©»Scan
π«Decrease size of lung nodules
Toxicities
π©π½ Patient β¬οΈ reduces dose of MET TKI due to edema
ππΌfeels well π
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD @oncoOuLungCA @MNagasaka 22/22 #TumorBoardTuesday #LCSM #LungCancer
π₯Bonusπ₯
π―If no targetable alteration then use chemotherapy +/- continue osimertinib
π§ Get brain MRI at time of disease progression for new baseline
π§²Especially if stopping osimertinib β‘οΈ MRI brain surveillance q6Month
π₯Bonusπ₯
π―If no targetable alteration then use chemotherapy +/- continue osimertinib
π§ Get brain MRI at time of disease progression for new baseline
π§²Especially if stopping osimertinib β‘οΈ MRI brain surveillance q6Month
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD #PostTest Q1οΈβ£ #TumorBoardTuesday #LungCancer
ππ½#CME Eval π integrityce.com
π€@MMarmarelis @norataranto taught us Tx after progression on Osimertinib, test your π§
π§What Tx?
57yo π©πΌβπ¦³
Asx Stage IV NSCLC adenocarcinoma
EGFR L858R
5 π§ mets <3mm
PD-L1 85%
ππ½#CME Eval π integrityce.com
π€@MMarmarelis @norataranto taught us Tx after progression on Osimertinib, test your π§
π§What Tx?
57yo π©πΌβπ¦³
Asx Stage IV NSCLC adenocarcinoma
EGFR L858R
5 π§ mets <3mm
PD-L1 85%
@TumorBoardTues @MMarmarelis @MPishvaian @JohnEbbenMDPhD @ADesaiMD @esinghimd @marinagarassino @n8pennell @LeciaSequist @apipervallillo @JessicaJLinMD @NarjustFlorezMD @Tony_Calles @JoelNealMD @DrSteveMartin @HosseinBorghaei @FawziAbuRous @Latinamd @CatherineShuMD @VivekSubbiah @DevikaDasMD @ShrutiPatelMD @CharuAggarwalMD @StephenVLiu @NIVokes @sands_jacob @JustinGainor @FordePatrick @DrRoyHerbstYale @DrRiyazShah @DrJNaidoo @Alfdoc2 @gbanna74 @bhsubecha @snoonanonc @debonco @bpiperdi @chase_wasson @acmoorephd @DrSanjayPopat @colinsky2k @alejos_david @jkverma2429 @steveleeyc @deeptibehl1 @SprakerMDPhD @BMuthusamyMD @AlexSpiraMDPhD #PostTest Q2οΈβ£ #TumorBoardTuesday
ππ½ Free CME π integrityce.com
ππ½#CME Eval π integrityce.com
π§ What treatment next?
57yo π©πΌβπ¦±
EGFR L858R NSCLC adenocarcinoma
ποΈ2 years osimertinib
π«Progress in lung
π¬Tissue re-biopsy
MET amp
ππ½ Free CME π integrityce.com
ππ½#CME Eval π integrityce.com
π§ What treatment next?
57yo π©πΌβπ¦±
EGFR L858R NSCLC adenocarcinoma
ποΈ2 years osimertinib
π«Progress in lung
π¬Tissue re-biopsy
MET amp
integrityce.com/TBT2023
Tumor Board Tuesday 2023 Conversations
Tumor Board Tuesdays is a regularly scheduled, Twitter-based case discussion forum led by expert fac...
integrityce.com/TBTeval23
Tumor Board Tuesday Evaluation 2023 (ID: i854/i855/i862/i865)
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