Alert 🎙Pharmacy Grand Rounds Thread Ahead! 🚨

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 Image
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 😔 Image
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 Image
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! Image
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 Image
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! Image
💊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) Image
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⚠️ ImageImage
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! ImageImage
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

✅Favors erdafitnib: uncontrolled DM, prefers oral tx, PN! Image
Thank you for viewing! Feel free to add your thoughts💭 about novel updates in mUC! #oncopharm #bladdercancer #immunoOncology #TwitteRx

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More from @theABofPharmaC

26 Apr
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🛑
Read 7 tweets
12 Mar
Urine Trouble: A review of Immune checkpoint inhibitor associated nephritis

See below some of the data I collected on this topic from a recent inservice! @OncoPharmPod #nephrotwitter #oncopharm
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 ☢️
Read 8 tweets
2 Sep 20
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 Image
Read 5 tweets
25 Aug 20
#OTILT #IDtwitter #oncopharm

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 😳🤯
Read 4 tweets
10 Aug 20
Mentor-Mentee SCCM CPP Spotlight: Dr. Andrea Newsome Sikora @AndreaSikora

“You should read better books.” 📚

The duality in this statement is a microcosm of mentorship:

You are enough right now & also you are capable of more.

An inspirational thread 👇🏻#PharmICU Image
Mentors have double vision. 👀

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 Image
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
Read 7 tweets
6 Aug 20
Abiraterone 💊 is an oral antiandrogen approved for metastatic hormone sensitive and castrate resistant prostate cancer

Why does abieraterone have to be coadministered with prednisone? 🤔 What if a patient wishes to avoid steroid therapy? 🤯

#oncopharm #pharmpearl
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 Image
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!
Read 4 tweets

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