Last week I had one of my final presentations of the year! With a catchy title😉
Urine for an Update! Updates in the management of metastatic urothelial cancer
Hold your bladders, this is an extensive update! 😂 #oncopharm
Bladder cancer can be divided into two ✌️subtypes: 1) Non-muscle invasive: encompasses in-situ and localized disease➡️5-yr OS >70%
2) Muscle invasive: encompasses regional or metastatic disease➡️5-yr OS dismal especially for metastatic disease 😔
Cisplatin=SOC
50% of pts w are ineligible due to older age👵🏻, poor PS, ⬇️ renal function, ⬇️hearing, neuropathy, heart failure 🫀& other comorbities that ⬆️ risk of ⚠️
Carboplatin yields inferior responses➡️NOT 🙅🏻♀️ an equal alternative due to ⬇️ OS😢➡️pt left w/minimal tx options
Luckily 👍🏼 there has been a tsunami 🌊 of new therapies approved for mUC in the recent decade: my presentation discussed the orange treatments in detail below!
1st: Pembro/Atezo to provide pts who are cisplatin inelidgble improved tx💊options
✅median OS > what we see 👀 with carbo (‼️indirect comparison‼️)
However an important POINT to CHECK(no pun intended)is PDL1 status➡️indicated only for PDL1+ pts unless ineligible for all chemo
The most predominant advancement in mUC is maintenance avelumab
JAVELIN Bladder 100➡️7 month improvement 🏆in OS compared to BSC➡️1st maintenance therapy for mUC!
Please 👀 advantages and disadvantages below!
💊1st targeted🎯tx for mUC‼️
Erdafitinib➡️pan-FGFR inhibitor❌approved for 2nd/3rd line mUC in for pts w/ susceptible FGFR3/2 genetic alterations
FGFR expressed in ~15% of mUC pts, studied in phase 2 trial BLC2001 ORR of 40% (improved ORR vs chemotherapy which yields~8-13% ORR)
One☝🏻cool😎 fact about erdafitnib➡️FGFR found in apical membrane of renal tubules➡️❌exchange of Phos/Na leading to hyperphosphatemia (👀👇🏻)
Interestingly🧐associated w/tx response😮
Dose titration req (8mg/d➡️14 days➡️9mg/d if phos <5.5mg/dL)
⚠️caution renal imp or hyperCa⚠️
Enfortumab-vedotin: antibody-drug conjugate🎯nectin-4 (expressed in 93% of mUC) bound to MMAE (microtubule distrusting agent🧬)
EV-301 phase 3 trial of EV in the 3L setting➡️30% RR for death 🤯
Ongoing studied looking at EV in earlier lines of tx & combined with immunotherapy!
Big AE to monitor for with EV are
1️⃣Hyperglycemia🍭(1💀 due to DKA on trial)
2️⃣ 👀disorders (dry eye, keratitis: Rx💊ocular steroid)
3️⃣Neuropathy: like brentuximab-VEDOTIN, the MMAE results in peripheral neurop
4️⃣Skin: nectin-4 expressed ubiquitously in skin➡️🔎 for SJS/TEN⚠️
How to decide between novel therapies? 🧐
✅Favors EV: retinal disorder (BBW for central serous retinopathy for erda), concern for adherence, absent FGFR (only found in 15%!), CKD/hyperCa due to hyperphosphatemia risk
What medications 💊 are should be avoided 🛑 or used with caution ⚠️ in patients with Myasthenia Gravis? 🤔
See 👀 the thread 🧵below⤵️ that summarizes an amazing grand rounds presentation by @UKPharmRes PGY1 @AliW_PharmD on key 🔑 medication considerations in MG
1️⃣Antibiotics to avoid or use w/caution🦠 💊
🛑FQs = FDA BBW for ⤴️ risk of MG crisis ➡️ avoid use if possible
⚠️ Macrolides ⤴️ rate of MG crisis (case reports)
⚠️ AG linked to ⤴️ ICU acquired weakness & exacerbate ‼️ MG crisis
📝Risk⬆️ w/neomycin vs. tobramycin & amikacin
Antibiotics considered to be SAFE alternatives to the above include
✅Beta-lactams
✅Tetracyclines
✅Linezolid
✅Bactrim
Ex. In an MG patient who presents 🏥 w/CAP 🫁 ➡️ choose ceftriaxone + doxycycline✅ OVER ceftriaxone + azithromycin🛑
Immune checkpoint inhibitors (ICI) ➡️revolutionized tx 💊 of various malignancies
✅Treatment that offers some pts🙋🏻♀️a chance of cure🤯
Also see a range of unique toxicities⚠️➡️autoimmune in nature
An emerging one of which is nephritis! (Insert a needed kidney emoji)
Pathogenesis of ICI-nephritis is unknown
Some hypothesis exist 🧐
✅stopping the breaks on the immune system results in excessive immune activation➡️ATIN
✅Previous renal insult or concurrent medications that lead to ATIN can accelerate the emergence of renal injury ☢️