Thread by @MPishvaian

@ShimaghavimiMD @TumorBoardTues #TumorBoardTuesday
Case 08/03/21

74 yo♂️presents with RUQ pain and fatigue, 30# weight loss, PS=2

CT scan demonstrates a large panc mass and diffuse liver metastases

Liver core biopsy confirms an acinar cell #PancreaticCancer

➡️What would be your treatment recommendation❓

@ShimaghavimiMD @TumorBoardTues #TumorBoardTuesday
08/03/21

He was treated with every other week Gem-nab-pac
🙏@GIcancerDoc
➡️Had rapid symptomatic improvement
➡️Now essentially normal PS
➡️Nice response to treatment for 9 months🙂

But then disease progression❗️

What would be your 2nd line therapy choice❓

@ShimaghavimiMD @TumorBoardTues @GIcancerDoc #TumorBoardTuesday
08/03/21

Germline NGS🧬testing did not reveal any inherited alterations

☝️Somatic (tumor) NGS🧬testing revealed a
💥BRAFV600E mutation💥

✅And no KRAS mutation

➡️Done while on 1st line therapy

Would the results alter your treatment choice now?

@ShimaghavimiMD @TumorBoardTues @GIcancerDoc #TumorBoardTuesday
Mini-Tweetorial 1/4

✅Many large NGS🧬assessments have➡️~25% of #Pancreaticcancers harbor “actionable” alterations❗️
📢i.e. - NOT RARE

E.g.
Lowery et al, pubmed.ncbi.nlm.nih.gov/28754816/
Pishvaian et al, pubmed.ncbi.nlm.nih.gov/29954777/
Aguirre et al,
pubmed.ncbi.nlm.nih.gov/29903880/

@ShimaghavimiMD @TumorBoardTues @GIcancerDoc #TumorBoardTuesday
Mini-Tweetorial 2/4

✅BRAF alterations found in 1 – 2% of all #pancreaticcancer
➡️Usually mutually exclusive of KRAS mut
➡️Enriched in acinar cell Ca

@DrHendifar @edikb @VivekSubbiah @kennamshaw @fp050392 @KlempnerSam @EmilyLyons87 @EileenMOReilly @Perthera

@ShimaghavimiMD @TumorBoardTues @GIcancerDoc @DrHendifar @edikb @VivekSubbiah @kennamshaw @fp050392 @KlempnerSam @EmilyLyons87 @EileenMOReilly @Perthera #TumorBoardTuesday
Mini-Tweetorial 3/4

🎯Targeting BRAFV600E-mutated cancers works!
✅ #colorectalcancer @skopetz BEACON
✅ #lungcancer Blanchard (Txed and Untxed)
✅ #BilaryCa @VivekSubbiah & Weinberg ROAR
✅Multiple reports in #PancreaticCancer

E.g.
pubmed.ncbi.nlm.nih.gov/31519698/

@ShimaghavimiMD @TumorBoardTues @GIcancerDoc @DrHendifar @edikb @VivekSubbiah @kennamshaw @fp050392 @KlempnerSam @EmilyLyons87 @EileenMOReilly @Perthera @skopetz #TumorBoardTuesday
Mini-Tweetorial 4/4

➡️3 types of targetable BRAF alterations in #PancreaticCancer
✅Exon 15 (eg BRAFV600E)
✅Exon 11 (eg BRAF N486_P490del)
✅RAF Fusions
⛔️"Kinase dead” mutations & mutations with confounding mutations (eg KRAS) do NOT respond to raf/mek Tx

@ShimaghavimiMD @TumorBoardTues @GIcancerDoc @DrHendifar @edikb @VivekSubbiah @kennamshaw @fp050392 @KlempnerSam @EmilyLyons87 @EileenMOReilly @Perthera @skopetz #TumorBoardTuesday
08/03/21
Patient outcome

✅Patient started on encoraf+binimet
➡️Did very well
➡️PR for 12 months

Shameless plug: PLEASE CONSIDER referring to our clinical trial of encoraf+binimet in BRAFV600E-mut #PancreaticCancer NCT04390243
✅Any # of prior lines of Tx

@ShimaghavimiMD @TumorBoardTues @GIcancerDoc @DrHendifar @edikb @VivekSubbiah @kennamshaw @fp050392 @KlempnerSam @EmilyLyons87 @EileenMOReilly @Perthera @skopetz #TumorBoardTuesday

Thank you all so much as usual! This was such an invigorating discussion. So much great input!