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 ☢️
I would like to make a few points of clarification for yesterday tweet on Vasopressin for cardiogenic shock.
🔑 point: Vasopressin is not “preferred” nor 1st line in CS but “may be considered” in select cases
Please read further thread 👇🏻👇🏻
It should have stated “may consider” VP as the suggestion of benefit in the JAHA article on CS was based on theoretical benefit and a ☝️ post hoc analysis of the VASST trial which included septic shock patients, notably a VERY different pathophys than CS. pubmed.ncbi.nlm.nih.gov/22518026/
Article did not also mention potential risk of harm from Vasopressin. (fluid retention, lack of inotropic activity, etc) and as @brentnreed pointed out, patients in this study required MORE inotropic support when vasopressin was used
What factors do you have to consider while treating a cancer pt with a malignant pleural effusion and concurrent infection? 🤔
1/ 🚨Cancer pts are at risk for MPE➡️consequence of metastatic involvement of the primary tumor in the pleura💨
💡Lung, breast, and lymphoma are the most common causes💡
Query of the pleural fluid with the use of the Lights criteria will help to determine the etiology (transudative or exudative)
Exudative=malignant OR infection
One of the criteria is a serum protein ratio >0.5
Since both MPE & infectious effusions🦠contain↗️↗️protein
🛑Avoid highly protein bound abx (Ex: daptomycin, ceftriaxone, ertapenem)➡️can get sequestered in the pleural fluid& have↘️systemic distribution & ↘️the ability to treat a bacteremia if present 😳🤯
Seeing you as you are and may be and celebrate the process of becoming.
Mentors are loyal to the person you are growing into, which reminds Dr. Sikora of Rumi:
“If you are irritated by every rub, how will you be polished?” #mentorship
We have a personal and professional responsibility to develop mentor-mentee relationships. 🤝
Dr. Sikora states “Mentorship has been a continuous lesson in the values of loyalty, humility, honesty, gratitude, balance, passion, discipline & integrity.” #gratitude
Abiraterone is a CYP17 inhibitor that suppresses downstream non-gonadal androgen synthesis
As a consequence➡️ reflex↗️↗️ ACTH production leads to excess in mineralocorticoids
Early trials WITHOUT pred▶️pts developed severe hypertension, hypokalemia and edema 2/2 ↗️ aldosterone
To suppress the reflex activation of the HPA axis & diminish symptoms of mineralocorticoid excess▶️coadministration with prednisone is required
If a pt is reluctant to taking long term pred▶️try Epleronone ✅ Mineralocorticoid receptor antagonist- blocks🛑 aldosterone!