Thread by @Latinamd

1/15 #TumorBoardTuesday #LungCancer #OncTwitter

83 yo👩🏽 remote 🚬 with good PS presents with SOB
PMhx: Afib, mild cognitive dysfunction
🩻: RML 6x3cm mass & pleural effusion
🫁: Stage IV lung adenocarcinoma
PDL1 90%

🎂Does age impact tx decision?
📊How would you Tx this pt?

@DrSteveMartin @glopesmd @NarjustDumaMD
@AnaVManana @COlazagasti @StephenVLiu @chulkimMD @LudaBazhenovaMD @benlevylungdoc @luisraez1 @edgardo_ny @GlopesMd

2/15 #TumorBoardTuesday

✅ Tissue NGS and💧liquid biopsy ordered
🔬Liquid biopsy comes with MET Ex 14 skip mutation
✅Confirmed with tissue NGS based assay (🧬RNA and 🧬DNA sequencing)

👉🏽Do you start 1L immunotherapy or 🎯therapy?

@CharuAggarwalMD @notahedge @JessicaJLinMD @LeciaSequist @DrJaimeLaurel @LudaBazhenovaMD @patrickreville @DrSanjayPopat @FordePatrick @DevikaDasMD @GRecondoMD @Anna_Minchom @Jbauml @DrViteri @UmbertoMalapel1 @JackWestMD @Dr_Ivanoncologo _ @AndresFCardonaZ @LuisERaez1

3/15 #TumorBoardTuesday #LungCancer
👩‍🏫Mini tweetorial 1

METex14 Mutation + #NSCLC Patient Characteristics

🫁3-4% of NSCLC
Adenocarcinoma (4%)
Squamous (2%)
Sarcomatoid (4-9%)
📌Typically older patients
📌Poor prognosis

👵>👴

🚬Smoker >>🚭 non smoker‼️

4/15 #TumorBoardTuesday
👩‍🏫Mini tweetorial 2

MET Ex 14 splicing error leads to
⬇️ubiquitination & degradation
⬆️MET kinase activity & proliferation

🕵️‍♀️MET Ex 14 skip alterations hard to detect b/o diff variants

🧬RNA🧪NGS help identify more Met ex skip muts missed with🧬assays

5/15 #TumorBoardTuesday #LCSM
👩‍🏫Mini tweetorial 3

Immunotherapy & MET:

METex14 may express ⬆️ PDL1 but inconsistent response to IO
( IO ORR ~20% and mPFS 2-4 months) depending on study

@NCCN rec: use MET inhibitor in 1st line

6/15 #TumorBoardTuesday #LCSM
👩‍🏫Mini tweetorial 4

PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered 🫁 cancers

📚PD-L1 expression 🔗 pubmed.ncbi.nlm.nih.gov/30165371/
📚Biomarkers testing pattern 🔗 pubmed.ncbi.nlm.nih.gov/35280795/

7/15 #TumorBoardTuesday
Back to our case🔎

👩🏽 Patient started on capmatinib 400mg BID (standard dose)
🩻Has almost a ✨complete response✨ on interim imaging at 2 months 🎉

Any considerations when treating elderly patients on targeted therapy?

▶️Increased side effects?
▶️Dose reduction?
▶️Diff Monitoring intervals?

@EnriqueSoto8 @COlazagasti #lcsm

8/15 #TumorBoardTuesday

🧲 2 months later: Interval scans at look great but patient reports leg edema and 20 lb weight gain.

🧐🧐🧐What could be happening??
🫀Drug-induced cardiomyopathy
🩸Deep vein thrombosis
💦METi peripheral edema

@HemOncFellows

@ShaalanBeg @drkpavithran @VivekSubbiah @esinghimd @mlazqui @RielyMD @SPSuehnholz @CDebyaniPhD @BairdAM @NReguart @geoff_oxnard @LaurenByersMD @SamuelKareffMD @AsaadTrabolsi @AnaVManana

9/15 #TumorBoardTuesday
👩‍🏫Mini tweetorial 5

METi Side Effects
Adverse Events in GEOMETRY-mono 1 (capmatinib) trial:

Peripheral Edema
All grades: 52%
Gr 3-4: 9%

Other: 😴, 🤮, dyspnea,⬇️appetite
SAEs: Interstitial🫁 Disease/Pneumonitis (1 death), Hepatotoxicity (3 dc drug)

9.5/15 #TumorBoardTuesday
👩‍🏫Mini tweetorial 5.5

Peripheral Edema is a METi class effect

VISION (Tepotinib) trial:

Edema
Gr 3: 9.4%
📌Irrespective of age, sex
📌higher in smokers, obese patients

📆Median to first onset edema- 8 weeks

10/15 #TumorBoardTuesday
👩‍🏫Mini tweetorial 6
METi Side Effects

👉🏽Edema most common reason for
🛑treatment
⬇️⬆️dose
❌dose

🕵️of MET inhibitor‐induced edema is still unclear
🧐Attributable to attenuation of HGF‐mediated signaling in peripheral vascular endothelium?

11/15 #TumorBoardTuesday
👩‍🏫Mini tweetorial 7

Edema Tx:
📍Be proactive (✅ weight)
Main Tx:
📍diuretics-brief relief
📍🛑cause agent
📍Change agent may work
🧢Capmatinib overcomes tepotinib‐induced intolerable🦵edema ncbi.nlm.nih.gov/pmc/articles/P…

lower🦵:NEJM nejm.org/doi/full/10.10…

12/15 #TumorBoardTuesday #LungCancer
👩‍🏫Mini tweetorial 8

Dosing in elderly:

⚠️Oral chemos have side effects‼️
⚠️Elderly at greater risk for side effects.
⚠️Must balance benefit of drug against side effects.

13/15 #TumorBoardTuesday
👩‍🏫Mini 9
MET TKIs classed by binding:
Type I (crizotinib, capmatinib, tepotinib, savolitinib)
➡️Capmatinib GEOMETRYMono-1 NEJM nejm.org/doi/full/10.10…
➡️Tepotinib VISION NEJM nejm.org/doi/full/10.10…
➡️Crizotinib PROFILE 1001 Nature nature.com/articles/s4159…

14/15 #TumorBoardTuesday
👩‍🏫Mini tweetorial 10
Type II MET inhibitors (cabozantinib, glesatinib, merestinib)

Resistance pathways may be primary or acquired and can vary by MET TKI Type.

New agents: Amivantamab (Phase 2, MET expansion cohort) …to be continued at #ASCO22

15/15 #TumorBoardTuesday #LungCancer #LCSM

🙏🏽Patient remains on Capmatinib 150mg BID (dose reduction)
🎉scans are stable with near CR
18 months since diagnosis

Using dosing lower than suggested 🧢 by trial/FDA approval, but still effective for patient.