Thread by @quirogad

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD 1/17 #TumorBoardTuesday #BreastCancer #OncTwitter @JasmineSukumar @DrGattiMays
👩🏽 65 yo post-menopausal
🚫comorbidities
🔺Triple-neg MBC, germline BRCA1 mut+, PD-L1 neg
👉On carbo/gem for 6 cycles

🩻NOW: Scans show progression in liver

🤨What 2L treatment do you recommend?

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays 2/17 #TumorBoardTuesday #bcsm

🤨 Poll: What percent of all people diagnosed with #BreastCancer carry a germline BRCA 1 and/or 2 mutation?

🤔Are there features that might make you more likely to suspect a patient is a mutation carrier?

@StoverLab @sardesai_sagar @OncoAlert

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert 3/17 #TumorBoardTuesday
👩🏽‍🏫Mini tweetorial 1👩🏻‍🏫

📌BRCA1/2 mutation

🔸Repair double-stranded breaks thru HRR
🔸Unable to fix 🧬 when damaged ➡️ add’l muts ➡️ cancer
🔸~5% of #BreastCancer;⬆️w/ TNBC
🔸Assoc w/ 40-65% of BC dx in 🚺, ≤ 9% in 🚹
📚science.org/doi/10.1126/sc…

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert 4/17 #TumorBoardTuesday
👩🏽‍🏫Mini tweetorial 2👩🏻‍🏫

📌BRCA1/2 mutation

🔸PARP➡️single-strand🧬damage repair protein
🔸Without BRCA1/2 mut➡️PARPi🚫kill tumor cells - DSB (ex BRCA) intact
🔸With BRCA1/2 mut➡️PARPi “double-hit” prevent🧬repair➡️tumor cell death
📚pubmed.ncbi.nlm.nih.gov/31931287/

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert 5/17 #TumorBoardTuesday #BRCA
👩🏽‍🏫Mini tweetorial 3👩🏻‍🏫

🇬🇷OLYMPIAD🇬🇷

🔸Phase III RCT olaparib vs physician’s choice chemo
🔸HER2-neg MBC
🔸Germline BRCA1/2 mut
🔸2 ≥ prior chemos
📚nejm.org/doi/full/10.10…
@MarkRobsonMD

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD 6/17 #TumorBoardTuesday
👩🏽‍🏫Mini tweetorial 4👩🏻‍🏫
🇬🇷OLYMPIAD🇬🇷
📍PFS 7.0 mo ola vs 4.2 mo chemo (HR 0.58)
📍RR 59.9% ola vs 28.8% chemo
✅Better safety/tolerability (≥ G3 AEs➡️ 37% olap / 51% chemo)
🔸OS analysis➡️19.3 mo ola vs 17.1 mo chemo (not stat sig)
📚pubmed.ncbi.nlm.nih.gov/30689707/

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD 7/17 #TumorBoardTuesday
👩🏽‍🏫Mini tweetorial 5👩🏻‍🏫
✨EMBRACA✨
🔸Ph III RCT talazoparib vs chemo
🔸HER2-neg MBC w/ gBRCA1/2 mut

Similar to
✨OLYMPIAD✨
📍PFS 8.6 mo tala vs 5.6 mo chemo
📍ORR 62.6% tala vs 27.2% chemo
✅Talaz ➡️better safety/tolerability
📚nejm.org/doi/full/10.10…

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD 8/17 #TumorBoardTuesday #BRCA
👩🏽‍🏫Mini tweetorial 6👩🏻‍🏫

🎉@US_FDA Olaparib👍🏽for gBRCA1/2 mut MBC (Jan 2018)
🎉Talazoparib 👍🏽 for gBRCA1/2 mut MBC (Oct 2018)

📍No restrictions which line of tx
🧪BRACAnalysis CDx test 👍🏽 as @US_FDA companion diagnostic
@drjennifergao @FDAOncology

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology 9/14 #TumorBoardTuesday #BRCA
👩🏽‍🏫Mini tweetorial 7👩🏻‍🏫

🏷@US_FDA drug labels 👇🏽

👍🏽Olaparib accessdata.fda.gov/drugsatfda_doc…
👍🏽Talazoparib accessdata.fda.gov/drugsatfda_doc…

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @drsarahsam @ravi770365 @thiago_apolinar @dradityabardia @drhburstein @drnavneet83 @hhampel1 @sidyadavmd @mabelonc @megaredd @sadia_ajaz @emilyfassi @gc_eileen @militazaheed @leandrojonatad1 @emmaasnyder19 @puxip @gbc02 @marleahdeank
@geneticsrach @thesarcasticowl @gcslaya

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @drkpavithran @caseofdees @jrgralow @lyndaweatherby @pozoparilli @stales @drznahleh @ian_portsmouth @obogler @g_villacampa @minouye271 @cathrynlewis @lgerratana
@ukbreasthealth @uk_oncologist @cgonzagaj @michaelmackley @draanacasas @meganlcook @theotherdrx @penaultllorca @tdcil

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @elmayermd @kellykhunt @liz_oriordan @ethansokol @drkellyphillips @StoverLab @JasmineSukumar @maryam_lustberg @DrGattiMays @ArielleMedford @RimapatelMD @rleonferre @sardesai_sagar @NicoleFleege

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology 10/17 #TumorBoardTuesday #BreastCancer
Back to our case🔎

👩🏽 Started olaparib 300mg twice daily

📆 4 weeks after starting:
🩸CBC
-ANC 400
-Hgb 8.0
(nml lab values prior to start)

🤢 Mild nausea

How would you manage?

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology 11/17 #TumorBoardTuesday #OncTwitter

📌Olaparib AEs

➡️ common & serious ⬅️

📍G ≥ 3
🩸anemia 16%
🩸neutropenia 9%
😴fatigue 3%

📍Any G
🤢nausea 58%
🤮vomiting 30%
🩸anemia 40%
🩸neutropenia 27%
😴fatigue 29%

📍Rare, but possibly fatal
🫁Pneumonitis 0.8%
🦴MDS/AML <1.5%

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology 12/17 #TumorBoardTuesday #BreastCancer
Back to our case🔎

Continued negative trends with blood counts
⬇️Dose reduce to 250mg twice a day
💊Nausea improved w/ ondansetron prn

Monitoring while on PARPi
🧪CBC, chemistries, LFTs monthly
🩻Imaging (CT/MRI/PET) every 3 months

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology 13/17 #TumorBoardTuesday
Quality of life 🙂

✅olaparib QoL ➡️ PARPi with improved #PROs over chemo
✅All sympt better than chemo, EXCEPT N/V
✅More pts with improved 🌎 health status/QoL (33.7% vs 13.4% chemo)
📚pubmed.ncbi.nlm.nih.gov/31446213/

Convenience & admin ➡️ most prefer PO 💊

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology 14/17 #TumorBoardTuesday
🧪BRCA germline test
📣Offer ALL pts with HER2-neg MBC📣

❗High risk early BC ➡️may qualify for adj PARPi if gBRCA mut
✨OlympiA✨3y iDFS➡️85.9% olap vs 77.1% placeb
📚nejm.org/doi/full/10.10…
🎉@US_FDA Adj olaparib👍🏽high-risk early gBRCA mut BC (Mar 22)

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @NTungMD @judygarber5 15/17 #TumorBoardTuesday
🧪BRCA germline genetic testing

📌Studies suggest high # BC pts want testing, but
🩺Dr didn’t recommend
💰Expensive
👨‍👩‍👧‍👦Family preference
📚jamanetwork.com/journals/jama/…
⚡️Discuss testing with experienced counselor!
⚡️Impacts other aspects of pt health & family

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @NTungMD @judygarber5 @reshmajagsi @AllisonKurian 16/17 #TumorBoardTuesday #BreastCancer #ClinicalTrials

🔮FUTURE olaparib use

✨TBCRC 048 - Olaparib Expanded trial
❓Does olaparib benefit extend to those with somatic BRCA1/2 mut and other DNA damage mutations?
❓Includes those with PALB2, ATM, CHEK2
📚 meetinglibrary.asco.org/record/185171

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @NTungMD @judygarber5 @reshmajagsi @AllisonKurian 17/17 #TumorBoardTuesday #BreastCancer

👩🏽remains on 250mg olaparib bid for 9 months
➡️ During followup, found to have tumor progression in liver

🤨What would next line therapy be?

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @NTungMD @judygarber5 @reshmajagsi @AllisonKurian #PostTest Q1️⃣ #TumorBoardTuesday
👉🏽CME Eval 🔗 integrityce.com/tbtEval
👉🏽ALL #CME🔗 integrityce.com/tbt

🤔 @jane_meisel @quirogad taught us 2L tx in BRCA1/2 muts #BreastCancer

Pt with PD-L1-neg, HR-, HER2- (IHC 0) met BC, BRCA+. 1L tx carbo/gem. What 2L tx would you pick?

@TumorBoardTues @jane_meisel @MPishvaian @JohnEbbenMDPhD @JasmineSukumar @DrGattiMays @StoverLab @sardesai_sagar @OncoAlert @MarkRobsonMD @US_FDA @drjennifergao @FDAOncology @NTungMD @judygarber5 @reshmajagsi @AllisonKurian #PostTest Q 2️⃣ #TumorBoardTuesday
👉🏽CME Eval 🔗 integrityce.com/tbtEval
👉🏽ALL #CME🔗 integrityce.com/tbt

🤔ALL patients with metastatic #BreastCancer and which of the following should be tested for BRCA mutations?