Thread by @rafee_talukder

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD 1/19 #TumorBoardTuesday #BladderCancer #OncTwitter

74 yo🧓🏼
HTN
DM2
2020: localized Rt upper tract urothelial carcinoma
2020: ✂️ radical nephroureterectomy
🧪Germline testing negative
Complicated by CKD stage 4 after ✂️ (creatinine clearance 25 ml/min)
🩻Restaging CT CAP 1 year

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD 🩻 NEW metastatic disease to spine, 🫁 and retroperitoneal lymph nodes
ECOG PS 2
🔬Biopsy of RP lymph node: Metastatic #UrothelialCarcinoma
🧪Molecular: FGFR3-TACC3 fusion, MTAP loss, CDKN2A loss

🤨 What 1L treatment would you pick for this patient?

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD 3/19 #TumorBoardTuesday @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD #UrothelialCancer

🤔 Is the above 74yo 🧓🏼 patient a good candidate for platinum-based chemotherapy?

🤨 Poll: Which of these criteria would make this patient platinum-ineligible?

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD 4/19 #TumorBoardTuesday #BladderCancer
👨🏽‍🏫Mini tweetorial 1👨🏻‍🏫

@MattGalsky criteria for cisplatin ineligibility in metastatic urothelial carcinoma
📚pubmed.ncbi.nlm.nih.gov/21555688/
@drrosenbergmsk
@JonAnker1

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 5/19 #TumorBoardTuesday
👨🏽‍🏫Mini tweetorial 2👨🏻‍🏫
✨KEYNOTE 052✨

Ph2: Cis-ineligible met #UrothelialCancer who have NOT initiated 1L systemic therapy.
📚ascopubs.org/doi/10.1200/JC…

Pembro: ONLY immune checkpoint inhibitor approved as 1L in plat-ineligible
📚ascopost.com/issues/septemb…

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 6/19 #TumorBoardTuesday

What thresholds should be used to define platinum ineligibility in #UrothelialCancer?
@shilpaonc Defining platinum-ineligible in patients with metastatic urothelial cancer
📚ascopubs.org/doi/abs/10.120…

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc 7/19 #TumorBoardTuesday
👨🏽‍🏫Mini tweetorial 3👨🏻‍🏫

Combo trials with ICI in platinum-ineligible
📚✨LEAP011: pembro/lenvatinib vs pembro/placebo: ascopubs.org/doi/abs/10.120…
📚✨BAYOU ascopubs.org/doi/abs/10.120…
📚✨EV-103, cohorts A & K ascopubs.org/doi/10.1200/JC…
📚oncologypro.esmo.org/meeting-resour…

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc 8/19 #TumorBoardTuesday #UrothelialCancer

🧓🏼started 1st line pembrolizumab (and zometa for bone mets)

💉 Completed 8 cycles
🩻 Restaging CT: progression of 🫁 mets and retroperitoneal lymphadenopathy

🤨 What 2L treatment do you recommend next?

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc 9/19 #TumorBoardTuesday
👨🏽‍🏫Mini tweetorial 4👨🏻‍🏫

✨EV-201 (Enfortumab vedotin)
📚 pubmed.ncbi.nlm.nih.gov/33991512/
✨TROPHY-U-01 (Sacituzumab govitecan)
📚 pubmed.ncbi.nlm.nih.gov/33929895/
✨BLC-2001 (Erdafitinib)
📚 nejm.org/doi/full/10.10…

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc 10/19 #TumorBoardTuesday #BladderCancer
👨🏽‍🏫Mini tweetorial 5👨🏻‍🏫

📌FGFR3 -oncogenic driver alteration

🔹FGFR3 alterations: 15-20% of metastatic bladder cancer
🔹FGFR3 alterations: 40-55% in upper tract UC

💉Erdafitinib: pan-FGFR (1-4) oral selective kinase inhibitor

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc 11/19 #TumorBoardTuesday
👨🏽‍🏫Mini tweetorial 6👨🏻‍🏫
💉Erdafitinib

👍🏽@US_FDA accelerated approval erdafitinib in platinum-refractory met #UrothelialCarcinoma with FGFR2/3 mut or fusion 19 (see figure👇🏽)

✨phase 3 THOR trial ongoing
📚annalsofoncology.org/article/S0923-…
🔗clinicaltrials.gov/ct2/show/NCT03…

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 12/19 #TumorBoardTuesday
👨🏽‍🏫Mini tweetorial 7👨🏻‍🏫

💉Erdafitinib AEs

🩸Hyperphosphatemia
🧑🏼‍🦲Alopecia
👄Stomatitis/dry mouth
🚽Diarrhea
🤢nausea
🧴💅Skin & nail change
🩸Anemia
👁️Ocular tox (central serous retinopathy, retinal pigment detach, dry 👁️)
😴Fatigue
✋🏽🦶🏽Hand-foot syndrome

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 13/19 #TumorBoardTuesday
👨🏽‍🏫Mini tweetorial 8👨🏻‍🏫

💉Erdafitinib

‼️Baseline comprehensive eye exam before tx‼️
👉🏽Monthly for 4 months
👉🏽 q3 months after or clinically necessary

FGFRi counters renal FGF-23 klotho axis🚥: ⬆️ vit D ➡️ hyperphosphatemia‼️

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 14/19 #TumorBoardTuesday
👨🏽‍🏫Mini tweetorial 9👨🏻‍🏫
💉Erdafitinib

Dosing
🟢Start 8mg qd
✅PHOSPHATE levels 2-3wks after start

WNML <5.5 ➡️increase to 9mg qd
btwn 5.5-7 ➡️continue at 8mg qd
>7: hold / reduce

serum phos
✅base
✅14-21d
✅monthly

⬇️Diet phos👉🏽consult RD
+phos bind?

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 15/19 #TumorBoardTuesday
Back to pt🔍

🧓🏼started enfortumab vedotin with partial response then progress
🔀carbo/gem with progress
🔀start erdafitinib 8mg daily

Ophthalmologic exam prior to initiating erda: normal

🧓🏼Now hyperphosphatemia at 2wk (6.5)
🤨what would you do?

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 16/19 #TumorBoardTuesday

🧓🏼 continues erdafinitb 8mg daily
🩸phosphate levels have stabilized to 5.2 at 1 month labs
🩻Restaging CT CAP ➡️ PR

BUT

📆 9 months later ➡️ progression

🤨 What would you use as third line therapy?

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 17/19 #TumorBoardTuesday

Choosing 1L, 2L, 3L can depend on
📍ECOG PS, age, comorbidities
📍AEs
📍Efficacy
📍Evidence
📍Clinician experience
📍Pt pref
📍Tx burden/convenience
📍administration route
📍Base symptoms
📍Compliance
📍Guides
#SharedDecision #InformedDecision

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 18/19 #TumorBoardTuesday

Do patients with FGFR3 mutation respond to ICI?
📚pubmed.ncbi.nlm.nih.gov/36601039/
📚pubmed.ncbi.nlm.nih.gov/31272788/

Combination FGFRi + ICI: additive effect? Merits further investigation
📚oncologypro.esmo.org/meeting-resour…

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri 19/19 #TumorBoardTuesday

🧓🏼 Patient started on Sacituzumab govitecan (with G-CSF) as 5L
🙏🏽 Partial response
📆 Continue treatment, labs during each infusion, & monitor AEs

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri #PostTest Q1️⃣ #CME #TumorBoardTuesday
👉🏽CME Eval 🔗 integrityce.com/tbtEval

🤔@PGrivasMDPhD @rafee_talukder taught us FGFR3 in #BladderCancer test your 🧠

🧐Which💊would U pick for a 74yoM w G2 neuropathy & FGFR3 mut+met bladder ca s/p gem-cis ➡️ maint avelumab

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri #PostTest Q2️⃣ #CME #TumorBoardTuesday
👉🏽ALL CME🔗 integrityce.com/tbt

🤔A patient presents with dry eyes and blurred vision while being on erdafitinib for treatment of metastatic #UrothelialCancer.

🧐What would be the most appropriate way to treat this patient?

@TumorBoardTues @PGrivasMDPhD @MPishvaian @JohnEbbenMDPhD @MattGalsky @DrRosenbergMSK @JonAnker1 @shilpaonc @US_FDA @montypal @brian_rini @DrYukselUrun @TiansterZhang @KidneyCancer @HHammersMD @arihakimi @RCCadvocate @AmandaNizamMD @QingZhangLab @DrRanaMcKay @DrScottHaake @DrDavidNanus @PavlosMsaouel @OAlhalabiMD @kcCURE @motzermd @MosheOrnsteinMD @neerajaiims @RenoHemonc @DrChoueiri Thank you for an engaging and informative #TumorBoardTuesday discussing FGFR3 alterations in metastatic urothelial ca

Post clinic tweetorial pic with the legendary @PGrivasMDPhD
@arkhaki @DRBakaloudiMD @DMakrakisMD @bcm_urology @BCMCancerCenter