@TumorBoardTues 1/17 #TumorBoardTuesday #bcsm
CASE: 55 yo post-menopausal 👩🏽
🚫comorbidities
HR+/HER2- MBC
🦴metastases, on letrozole+palbociclib 2 yrs
🩻Scans: progression in liver
🔬Liver biopsy: ER 90% PR 90% HER2- (IHC 1+)
Tissue NGS➡️ESR1 & PIK3CA mutation
🤨What 2L tx do you recommend?
CASE: 55 yo post-menopausal 👩🏽
🚫comorbidities
HR+/HER2- MBC
🦴metastases, on letrozole+palbociclib 2 yrs
🩻Scans: progression in liver
🔬Liver biopsy: ER 90% PR 90% HER2- (IHC 1+)
Tissue NGS➡️ESR1 & PIK3CA mutation
🤨What 2L tx do you recommend?
@TumorBoardTues 2/17 #TumorBoardTuesday #BCSM #OncTwitter
🤨 What is the prevalence of PIK3CA activating mutations in metastatic HR+/HER2- breast cancer?
@Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert
🤨 What is the prevalence of PIK3CA activating mutations in metastatic HR+/HER2- breast cancer?
@Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert 3/17 #TumorBoardTuesday
👩🏽🏫Mini tweetorial 1👩🏻🏫
🔸⬆️PI3K/Akt/mTOR pathway➡️cell proliferation, growth & survival
🔸Class I PIK3 proteins have catalytic subunit (p110)
🔸p110 contains 4 isoforms: α, β, γ, δ
🔸p110α mut (PIK3CA encoded)➡️ resistance to ET
📚pubmed.ncbi.nlm.nih.gov/31828441/
👩🏽🏫Mini tweetorial 1👩🏻🏫
🔸⬆️PI3K/Akt/mTOR pathway➡️cell proliferation, growth & survival
🔸Class I PIK3 proteins have catalytic subunit (p110)
🔸p110 contains 4 isoforms: α, β, γ, δ
🔸p110α mut (PIK3CA encoded)➡️ resistance to ET
📚pubmed.ncbi.nlm.nih.gov/31828441/
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo 4/17 #TumorBoardTuesday
👩🏽🏫Mini tweetorial 2 👩🏻🏫
📌prevalence of PIK3CA activating mutation in HR+ ABC👉🏽~40%
🔸non isoform-specific PI3K inhibitors w low on-target effect & toxicities🙅🏽♀️
Ex: Pictilisib,Buparlisib
🔸Alpelisib: PI3Kα-selective inhibitor & degrader ➡️ less toxic👍🏽
👩🏽🏫Mini tweetorial 2 👩🏻🏫
📌prevalence of PIK3CA activating mutation in HR+ ABC👉🏽~40%
🔸non isoform-specific PI3K inhibitors w low on-target effect & toxicities🙅🏽♀️
Ex: Pictilisib,Buparlisib
🔸Alpelisib: PI3Kα-selective inhibitor & degrader ➡️ less toxic👍🏽
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo 5/17 #TumorBoardTuesday
👩🏽🏫Mini tweetorial 3 👩🏻🏫
✨SOLAR-1✨
🔸phase III RCT alpelisib + fulvestrant vs fulvestrant
🔸post-menopausal #MBC
🔸1 prior line of ET (AI)
🔸PIK3CA mutated & non-mutated cohorts
📚nejm.org/doi/pdf/10.105…
👇🏽#ESMO20 @FAndreMD
👩🏽🏫Mini tweetorial 3 👩🏻🏫
✨SOLAR-1✨
🔸phase III RCT alpelisib + fulvestrant vs fulvestrant
🔸post-menopausal #MBC
🔸1 prior line of ET (AI)
🔸PIK3CA mutated & non-mutated cohorts
📚nejm.org/doi/pdf/10.105…
👇🏽#ESMO20 @FAndreMD
https://twitter.com/prat_aleix/status/1307341573764636672?s=20&t=_LdOQg23R9whwybTGJ0LsA
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad 6/17 #TumorBoardTuesday #BCSM
👩🏽🏫Mini tweetorial 4 👩🏻🏫
✨SOLAR-1✨
🌞PIK3CA mutation results
📍PFS ⬆️ 5.3 mo (HR 0.65, p<0.001)
📍OS ⬆️ 7.9 mo (HR 0.86, p=0.15)
✅benefit across subgroups
❌PIK3CA non-mutated no benefit
📚annalsofoncology.org/article/S0923-…
👩🏽🏫Mini tweetorial 4 👩🏻🏫
✨SOLAR-1✨
🌞PIK3CA mutation results
📍PFS ⬆️ 5.3 mo (HR 0.65, p<0.001)
📍OS ⬆️ 7.9 mo (HR 0.86, p=0.15)
✅benefit across subgroups
❌PIK3CA non-mutated no benefit
📚annalsofoncology.org/article/S0923-…
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad 7/17 #TumorBoardTuesday
🎉@FDA & @EMA_News approval PIK3CA-mutated HR+ HER2- ABC after 1L ET
📍FDA approved CDx (tumor tissue or plasma ctDNA)
🧪Qiagen therascreen PIK3CA RGQ PCR Kit
🧪NGS with @FoundationOne Tissue & Liquid CDx
🏷drug label 👇🏽
accessdata.fda.gov/drugsatfda_doc…
🎉@FDA & @EMA_News approval PIK3CA-mutated HR+ HER2- ABC after 1L ET
📍FDA approved CDx (tumor tissue or plasma ctDNA)
🧪Qiagen therascreen PIK3CA RGQ PCR Kit
🧪NGS with @FoundationOne Tissue & Liquid CDx
🏷drug label 👇🏽
accessdata.fda.gov/drugsatfda_doc…
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne 8/17 #TumorBoardTuesday #BreastCancer
🕵🏻♀️There’s several platforms for detecting PIK3CA activating mutation in real world practice
📊Which 🧬 genomic profiling test do YOU most commonly use in practice?
🕵🏻♀️There’s several platforms for detecting PIK3CA activating mutation in real world practice
📊Which 🧬 genomic profiling test do YOU most commonly use in practice?
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne 9/17 #TumorBoardTuesday
🧐If PIK3CA mutation NOT detected in plasma ctDNA, next step❓
‼️Tumor tissue testing‼️
📌ctDNA assay less sensitive➡️possibly miss druggable 🎯
🌞SOLAR 1: 40% of PIK3CA non-altered by ctDNA had PIK3CA mutation detected in tissue
🧐If PIK3CA mutation NOT detected in plasma ctDNA, next step❓
‼️Tumor tissue testing‼️
📌ctDNA assay less sensitive➡️possibly miss druggable 🎯
🌞SOLAR 1: 40% of PIK3CA non-altered by ctDNA had PIK3CA mutation detected in tissue
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne 10/17 #TumorBoardTuesday #BreastCancer
📆When is the ideal time to test for PIK3CA mutation❓
🧪Test in HR+ MBC at diagnosis or after CDK4/6i progression
🔸BYLieve cohort A: 👉🏽 alpelisib benefit after CDK4/6i+AI (median PFS 7.3 mo)
📚@hoperugo thelancet.com/journals/lanon…
📆When is the ideal time to test for PIK3CA mutation❓
🧪Test in HR+ MBC at diagnosis or after CDK4/6i progression
🔸BYLieve cohort A: 👉🏽 alpelisib benefit after CDK4/6i+AI (median PFS 7.3 mo)
📚@hoperugo thelancet.com/journals/lanon…
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne 11/17 #TumorBoardTuesday
Back to our case🔎
👩🏽 Started alpelisib 300mg + fulvestrant for PIK3CA E545K activating mutation
2 week f/u:
💩 Developed G2 diarrhea
🙌🏽 improved with loperamide 2mg BID
🚰 new polyuria
🍭 Fasting Blood sugars ⬆️⬆️ 200s
(baseline normal)
Back to our case🔎
👩🏽 Started alpelisib 300mg + fulvestrant for PIK3CA E545K activating mutation
2 week f/u:
💩 Developed G2 diarrhea
🙌🏽 improved with loperamide 2mg BID
🚰 new polyuria
🍭 Fasting Blood sugars ⬆️⬆️ 200s
(baseline normal)
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne 12/17 #TumorBoardTuesday #BCSM
👩🏽🏫Mini tweetorial 5 👩🏻🏫
Alpelisib AEs
➡️ common & serious ⬅️
📍G ≥ 3
🍭hyperglycemia 37%
👺rash 10%
💩diarrhea 7%
📍Any G
💩diarrhea 60%
👺rash 35%
🍭hyperglycemia 65%
🫁pneumonitis 1.8%
🤢nausea 45%
👩🏽🏫Mini tweetorial 5 👩🏻🏫
Alpelisib AEs
➡️ common & serious ⬅️
📍G ≥ 3
🍭hyperglycemia 37%
👺rash 10%
💩diarrhea 7%
📍Any G
💩diarrhea 60%
👺rash 35%
🍭hyperglycemia 65%
🫁pneumonitis 1.8%
🤢nausea 45%
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne 13/17 #TumorBoardTuesday
👩🏽🏫Mini tweetorial 6 👩🏻🏫
🍭Hyperglycemia
🔸Mechanism
🚧inhibition of PIK3 in liver & skeletal muscle impairs insulin signaling
⚠️Risk factors
✅BMI ≥25
✅hgbA1c ≥5.7%
👉🏽optimize metabolic health prior to tx
📚 ascopubs.org/doi/abs/10.120…
👩🏽🏫Mini tweetorial 6 👩🏻🏫
🍭Hyperglycemia
🔸Mechanism
🚧inhibition of PIK3 in liver & skeletal muscle impairs insulin signaling
⚠️Risk factors
✅BMI ≥25
✅hgbA1c ≥5.7%
👉🏽optimize metabolic health prior to tx
📚 ascopubs.org/doi/abs/10.120…
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne 14/17 #TumorBoardTuesday
👩🏽🏫Mini tweetorial 7👩🏻🏫
Hyperglycemia Tx
✅lifestyle changes
✅endocrinology consult
✅metformin or insulin sensitizer (eg.TZD, DPP4 inhibitor)
Novel studies underway
📚ascopubs.org/doi/abs/10.120…
TIFA trial @Neil_Iyengar @SherryShenMD clinicaltrials.gov/ct2/show/NCT05…
👩🏽🏫Mini tweetorial 7👩🏻🏫
Hyperglycemia Tx
✅lifestyle changes
✅endocrinology consult
✅metformin or insulin sensitizer (eg.TZD, DPP4 inhibitor)
Novel studies underway
📚ascopubs.org/doi/abs/10.120…
TIFA trial @Neil_Iyengar @SherryShenMD clinicaltrials.gov/ct2/show/NCT05…
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne @Neil_Iyengar @SherryShenMD 15/17 #TumorBoardTuesday
👩🏽🏫Mini tweetorial 8👩🏻🏫
Alpelisib other AEs
➡️supportive care⬅️
💩Diarrhea
💊antimotility agents
👺Rash
💊prophylactic antihistamines‼️
🥼consider derm c/s
🧴topical or systemic steroids
FDA label👇🏽
👩🏽🏫Mini tweetorial 8👩🏻🏫
Alpelisib other AEs
➡️supportive care⬅️
💩Diarrhea
💊antimotility agents
👺Rash
💊prophylactic antihistamines‼️
🥼consider derm c/s
🧴topical or systemic steroids
FDA label👇🏽
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne @Neil_Iyengar @SherryShenMD @EthanSokol @ValsamoA @gary_lyman @LiangRhea @MdVarvaras @Lucarecco @BianchiniGP 16/17 #TumorBoardTuesday
Back to our case🔎
👩🏽met w dietitian & diabetologist
✅started metformin 500mg BID w uptitration to 1000mg BID
✅remained on alpelisib 300mg
👍🏽Fasting glucose improved: 90-110
✨Restaging @ 3 mo ➡️ tx response w liver mets regression
Back to our case🔎
👩🏽met w dietitian & diabetologist
✅started metformin 500mg BID w uptitration to 1000mg BID
✅remained on alpelisib 300mg
👍🏽Fasting glucose improved: 90-110
✨Restaging @ 3 mo ➡️ tx response w liver mets regression
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne @Neil_Iyengar @SherryShenMD @EthanSokol @ValsamoA @gary_lyman @LiangRhea @MdVarvaras @Lucarecco @BianchiniGP 17/17 #TumorBoardTuesday #BreastCancer
🔥Bonus Poll🔥
🔸After 6 months, there is disease progression. Liver function tests remain within normal limits
🤨 Following progression on alpelisib + fulvestrant, what is your next treatment recommendation?
🔥Bonus Poll🔥
🔸After 6 months, there is disease progression. Liver function tests remain within normal limits
🤨 Following progression on alpelisib + fulvestrant, what is your next treatment recommendation?
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne @Neil_Iyengar @SherryShenMD @EthanSokol @ValsamoA @gary_lyman @LiangRhea @MdVarvaras @Lucarecco @BianchiniGP #PostTest Q1️⃣ #TumorBoardTuesday
👉🏽CME Eval 🔗: integrityce.com/tbtEval
🤔 @maryam_lustberg @JasmineSukumar taught us PIK3CA #BreastCancer treatment, test your 🧠 with 2❓
🧐 What would be your next step if a PIK3CA mutation wasn’t detected in plasma?
👉🏽CME Eval 🔗: integrityce.com/tbtEval
🤔 @maryam_lustberg @JasmineSukumar taught us PIK3CA #BreastCancer treatment, test your 🧠 with 2❓
🧐 What would be your next step if a PIK3CA mutation wasn’t detected in plasma?
@TumorBoardTues @Dr_RShatsky @PTarantinoMD @hoperugo @NicoleKuderer @StoverLab @CarmenCalfa @sardesai_sagar @stolaney1 @OncoAlert @JavierCortesMD @DrHBurstein @drenriquegrande @RICKLIN4TH @ProfWishart @ProfAMThompson @oncoplastics @Liz_ORiordan @DrJNaidoo @FAndreMD @SorenBentzen @prat_aleix @JaniceTNBCmets @abhenilmittal @seiichi_mori @jansen_marnix @ValerieTeng @MeriemMakhlou11 @quirogad @FDA @EMA_News @FoundationOne @Neil_Iyengar @SherryShenMD @EthanSokol @ValsamoA @gary_lyman @LiangRhea @MdVarvaras @Lucarecco @BianchiniGP @maryam_lustberg #PostTest Q2️⃣ #CME #TumorBoardTuesday
👉🏽Free CME🔗: integrityce.com/tbt
👨🏽🦳Male who has stage 4 (M1) #BreastCancer with tumor HR+/HER2- & PIK3CA mutation, previously tried aromatase inhibitor + a GnRH analog + ribociclib.
🧐What therapy would YOU recommend?
👉🏽Free CME🔗: integrityce.com/tbt
👨🏽🦳Male who has stage 4 (M1) #BreastCancer with tumor HR+/HER2- & PIK3CA mutation, previously tried aromatase inhibitor + a GnRH analog + ribociclib.
🧐What therapy would YOU recommend?
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