Thread by @ArielleMedford

@TumorBoardTues 1/19 #TumorBoardTuesday #BreastCancer #OncTwitter

45yo 👩🏼 non smoker 🚭 with 2 kids is diagnosed with T2N0 TNBC
Fmh: mother (78) HTN, grandmother BRCA+
🧪Genetic testing shows BRCA1 mutation

🤨How would you proceed?

@TumorBoardTues 2/19 #TumorBoardTuesday #TNBC
Rxed with Neoadj AC-T (IO not approved at time), followed by B/L mastectomy.

🔬Pathology showed 5mm residual disease.

IDC
ER 0%
PR 0%
HER2 0
Ki-67 90%
Stage ypT1aN0

She receives adjuvant capecitabine.
@dradityabardia @MPishvaian @JohnEbbenMDPhD

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD 3/19 #TumorBoardTuesday #BreastCancer #BCSM
🗓 Two years after completing capecitabine, she’s found to have liver metastases.

🔬 Bx: TNBC, PD-L1+

🤨 What would you do next?
🤨 Would your decision change if she had received neo/adjuvant pembrolizumab?

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD 4/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 1👩🏼‍🏫

FIRST…

First-Line Treatment for Metastatic TNBC

✨PD-1 & PD-L1 inhibitors✨

👉@FDA accelerated approval of atezolizumab for PD-L1+ unresectable locally advanced or metastatic TNBC (IMpassion 130 Trial)

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 👨🏽‍🏫Mini tweetorial 2👩🏼‍🏫

First-Line Tx for Metastatic TNBC

✨PD-1 & PD-L1 inhibitors✨

👉🏼Approval contingent on confirmatory IMpassion131 trial.

PD-L1+ population:
Median PFS 7.5 vs 5 mo (HR 0.62)
OS 25.0 vs 15.5 mo (HR 0.62) <- significant!

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 6/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 3👩🏼‍🏫

BUT WAIT…

✨Impassion 131✨

First-Line Tx for Metastatic TNBC

⚠️FDA issues alert about efficacy & potential safety 😰 of atezolizumab in combo with paclitaxel for the treatment of #BreastCancer.

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 7/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 4👩🏼‍🏫

AND…

✨Impassion 131✨

First-Line Tx for Metastatic TNBC

⚠️ Primary endpoint PFS not met‼️

❌Accelerated approval of atezolizumab voluntarily withdrawn.👎🏽

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 8/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 5👩🏼‍🏫

THEN…

✨Keynote 355✨
PD-L1+ = CPS 10
Pembro + chemo vs Placebo + chemo (chemo = paclitaxel, nab-paclitaxel, or gem/carbo)
PFS in PD-L1+ ➡️9.7 vs 5.6 (HR 0.65)

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 9/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 6👩🏼‍🏫

✨Keynote 355✨

First-Line Tx with Pembrolizumab for Metastatic TNBC

👉Nov, 20: FDA approves pembrolizumab for PD-L1+ mTNBC 👏🏼

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 10/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 7👩🏼‍🏫
What about PARPi in gBRCA mut #BreastCancer?
👍🏽Olaparib improves outcomes for patients w/ gBRCA mutant MBC
📚nejm.org/doi/full/10.10…
👍🏽Talazoparib improves outcomes for patients w/ gBRCA mutant MBC
📚nejm.org/doi/full/10.10…

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 11/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 8👩🏼‍🏫

PARP inhibitor & Overall Survival in BRCA mut MBC

Olaparib vs chemo (OlympiaD)
PFS 7.0 vs 4.2 mo (HR 0.58), no sig improvement in OS

Talazoparib vs chemo (EMBRACA)
PFS 8.6 vs 5.6 mo (HR 0.54), no sig improvement in OS

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 12/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 9👩🏼‍🏫

🤔So how do you choose IO vs. PARPi for 1st line treatment of BRCA mutant PD-L1+ mTNBC?
📚

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA 13/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 10👩🏼‍🏫

🧐Choosing - IO vs. PARPi for 1st line tx of BRCA💥mutant💥mTNBC?

📖Adapted for @ASCO & @myESMO Keenan J et al.
Try this algorithm👇🏽👇🏽

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA @ASCO @myESMO 14/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 11👩🏼‍🏫

🤨Would adding PD-1i to PARPi improve outcomes?

Anti-PD-1 activity depends on:
📍Generating productive immune response
📍Effective Ag presentation
📍T‑cell priming
📍Tumor infiltration
📍Recognizing, killing tumor cells

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA @ASCO @myESMO 15/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 12👩🏼‍🏫

📌 PARPi and PD-(L)1i have complimentary MOAs

✅PARP inhibitors prevent 🧬 DNA repair ⏩ promotion of 🔥inflammation & priming of immune response

✅Increase effective recognition & infiltration of tumors by immune cells

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA @ASCO @myESMO 16/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 13👩🏼‍🏫

📌 PARPi and PD-(L)1i have complimentary MOAs

✅PARPi treatment ⏩ 2-3X ⬆️expression of PD‑L1 by tumor cells

🐁Mouse studies demonstrate significant ⬆️in OS with combo, but NOT with each agent alone

👇🏽See figure👇🏽

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA @ASCO @myESMO 17/19 #TumorBoardTuesday #BCSM
👨🏽‍🏫Mini tweetorial 14👩🏼‍🏫

✨KEYLYNK-009✨

✅PD-L1+ TNBC
+
✅BRCAmut
✅1st line adv/met TNBC
✅Carbo/gem + pembro

🫧THEN🫧
✅Continue carbo/gem + pembro

🫧OR🫧
➡️pembro + olaparib

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA @ASCO @myESMO 18/19 #TumorBoardTuesday #BreastCancer #OncTwitter
💫Recap💫

🥇1st Line:
Chemo & pembro is preferred for PD-L1➕mTNBC

🥈2nd Line:
PARPi (olap, tala) is SOC for BRCA-mut mTNBC

Sacituzumab govitecan otherwise SOC

🥉3rd Line:
Chemo (capecitabine, eribulin) is SOC

@TumorBoardTues @dradityabardia @MPishvaian @JohnEbbenMDPhD @FDA @ASCO @myESMO 19/19 #TumorBoardTuesday #BreastCancer
Back to our case🔎

👩🏼 Started on carboplatin/gem + pembro
🗓 1 year later on same treatment
🩻 Undergoes regular interval CT scans
👩🏼‍🌾 Back to gardening & playing tennis 🎾