Jonathan Riess, MD MS

Medical Director Thoracic Oncology
UC Davis Comprehensive Cancer Center

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Great to see the progress made and excited about the future!

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Yes and we generally test squamous too - especially patients with never or light smoking history or scant tissue. Sometime we find EGFR mutations, HER2 mutations etc in squamous lung cancers.

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Great case, presentation and discussion!

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange accrual outside USA

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Activity in early stage/locally advanced HER2 mutated NSCLC an importhant question. Especially like EGFR these cancers tend not to be responsive to IO.

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Next steps: 1) understanding and overcoming resistance, 2) rational combination therapies to enhance efficacy 3) improving on CNS activity.

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Still early days but unclear activity of sevabertinib after zongertinib. Would still expect TDX-d to work by mechanism but differences in clinical outcomes of TDX-d after HER2 TKI TBD.

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange No clear differences in clinical activity in the studies. Zongertinib is EGFR wild type sparing which has implications for on target EGFR toxicity like diarrhea.

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Good question. No prior treated means chemo, IO etc. Not other anti HER2 TKI.

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Yes for oligoprogressive disease, but not for diffuse PD.

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Still much more to learn about HER2 TKI resistance mechanisms and how to overcome them.

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange In NSCLC classic non-smoking oncogene driver similar to EGFR. As oppossed to overexpression of HER2 which is much more heterogeneous.

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE There might be. Anecdotally, heterogeneous responses to IO in HER2 overexpression. Some act like EGFR mutant and don't respond and others appear more sensitive.

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Several new approvals. Zongertinib for 1L in metastatic HER2 activating TKD mutation, sevabertinib for HER2 activating mutation on top of approval of TDXd for activating HER2 mutations. Exciting times!

[Jonathan Riess, MD MS @riess_md]

@JackieAredoMD @TumorBoardTues @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange Concurrent increases detection rate. Just plasma runs risk of false negative, especially in M1A (pleura and lung only) disease.

[Jonathan Riess, MD MS @riess_md]

@MPishvaian @JackieAredoMD @TumorBoardTues @IntegrityCE Unclear benefit of IO in HER2 mutation. I do give in HER2 overexpressed NSCLC though. Many of the phase 3 trials include chemo-IO as control since HER2 not excluded from KN189.

[#TumorBoardTuesday @TumorBoardTues]

#TumorBoardTuesday
In #NSCLC, targeting🎯HER2 is more than just ⬆️protein expression. DNA🧬alterations are key🔑too‼️

📢Join us Tuesday, 03-10-26 at 8PM ET as @riess_md & @JackieAredoMD🗣️HER2 targeted strategies in mNSCLC

RT and bring others into the discussion‼️