Lightnews — Scholar-powered news

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Mar 19

Excited to present "AI for precision oncology: Real-world analysis of a CDK4/6 inhibitor model" with @akshatsinghal.bsky.social at #ACSSpring2025 this weekend! Love sharing our work with different crowds!

1 2

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

It was so awesome to be part of this @tumorboardtuesday.bsky.social opportunity with @dr-rshatsky.bsky.social and to discuss this hot topic! Also grateful for Dr. Shatsky's mentorship, as I join our amazing breast oncology team at UCSD this Sep! I am the lucky one, and so excited!

Dr. RShatsky @dr-rshatsky.bsky.social · Jan 15

I also just want to thank my amazing fellow @zoezhang.bsky.social for this super informative Sky Chat and announce to the world that my team is super excited that she will be joining us at UCSD Breast Medical Oncology as faculty in Sept!!! We are very lucky! @ucsdhealthsci.bsky.social

2

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

#PostTest Q2️⃣ #TumorBoardTuesday
👉🏽 Free CME 🔗 integrityce.com/TBT2024

Which is likely to be optimal for HR+ mBC that progresses after 1Y of 1L ribociclib + AI and harbors an ESR1 Y537S mutation?
Abemaciclib + fulvestrant
Imlunestrant + abemaciclib
Elacestrant
Capivasertib + fulvestrant

Tumor Board Tuesday 2024 - Integrity CE

Tumor Board Tuesdays is a regularly scheduled, Twitter-based case discussion forum led by expert faculty exploring cases in various solid tumor malignancies. The series will focus on practice applicat...

integrityce.com

2 3

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

#PostTest Q1️⃣ #TumorBoardTuesday
👉🏽#CME Eval 🔗 integrityce.com/TBTeval24
👉🏽ALL CME🔗 integrityce.com/TBT2024

Per INAVO120 data in ET-refractory, PIK3CA+ HR+ la/mBC, adding inavolisib to palbociclib + fulvestrant improved mPFS to:
9 months
12 months
15 months
18 months

2024 Tumor Board Tuesday Evaluation

Take this survey powered by surveymonkey.com. Create your own surveys for free.

integrityce.com

1 2 3

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

20/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
🔑points
👉Novel ET are changing trt landscape for ER+/HER2- ABC
🤔W/ expanding options, come opportunities and challenges
➡️Many burning questions: Sequencing therapy, new combinations (ie CDK4/6i+SERDs)...

a little girl is crying and holding her fist in the air with the word exciting written on the bottom .

ALT: a little girl is crying and holding her fist in the air with the word exciting written on the bottom .

media.tenor.com

3 2 4

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

19/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
👉For instance: Feb 2024, ARV-471, an investigational, oral PROTAC studied in the phase 3 VERITAC-2 trial, received FDA fast-track designation.
www.pfizer.com/news/announc...

Arvinas and Pfizer’s Vepdegestrant (ARV-471) Receives FDA Fast Track Designation for the Treatment of Patients with ER+/HER2- Metastatic Breast Cancer | Pfizer

Vepdegestrant is an investigational PROteolysis Targeting Chimera (PROTAC®) protein degrader designed to target and degrade the estrogen receptor (ER) protein

www.pfizer.com

2 4 6

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

18/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
Beyond SERDs/SERMs…novel endocrine therapies targeting other mechanisms in pipeline:
Proteolysis targeting chimeras (PROTACs), selective ER covalent antagonists, complete ER antagonists just to name a few!🤯

4 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

17/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
Beyond EMBER-3, novel combinations with SERDs and SERMs also being evaluated with CDK4/6i

1 4 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

17/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
➡️Multiple novel SERDS studied in HR+/HER2- ABC
👍Elacestrant currently remains the only FDA approved option
🚧Novel SERDs w/ unique AEs from fulvestrant
⚡This is a rapidly changing landscape!

1 3 8

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

16/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
🔙 to our case
EMBER3 would be a great option, but based on availability, pt got elacestrant
🚫 abema+fulvestrant:
-ESR1 Y537S 👉fulvestrant resistance.
-POSTMONARCH👉modest PFS benof abema+fulv vs placebo+fulv AND 🚫benefit in subgroup w/ prior ribo

1 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

15/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
👩‍⚕️Mini Tutorial 6👩‍⚕️
Imlunestrant: favorable safety profile vs SoC. Dc rate: 4%
Imlun+abema: diarrhea=most common AE, all grade: 86%, grade≥3: 8%. Dc rate: 6%
No 👁️or 💙AE signals like in other oral SERDS (i.e. photopsia, bradycardia in camizestrant)

3 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

14/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
👩‍⚕️Mini Tutorial 5👩‍⚕️
🔑Findings:
PFS ESR1m: 5.5 (Imlun) vs 3.8 mon (SoC). HR= 0.62, p<0.001
PFS all: 9.4 (Imlun+abema) vs 5.5 mon (imlun). HR=0.57, p<0.001
Benefit of imlun+abema in key subgroups: ESR1m, PIK3CAm, visceral disease, prior CDK4/6i

1 4 6

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

13/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
👩‍⚕️Mini Tutorial 4👩‍⚕️
Novel, oral SERDs in development w/ ⬆️efficacy ⬇️toxicities
👉💡imlunestrant, studied in the EMBER-3 trial presented at #SABCS24
🔑Pt features:
~37% with ESR1m, ~40% with PIK3CAm, >50% visceral disease
👉1/3 adj ET, 2/3 prior CDK4/6i

3 4 6

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

12/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
2023, FDA approved elacestrant based on the EMERALD trial
Pts: prior 1-2L ET, ≤1 chemo for ABC: R 1:1 ➡️elacestrant vs SoC
➡️
PFS all: HR = 0.70; p = .002
PFS ESR1m: HR = 0.55; p = .0005
Benefit in key subgroups: PIK3CA mut, ESR1 mut, and TP53 mut

1 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

11/20 #TumorBoardTuesday @dr-rshatsky.bsky.social
👩‍⚕️Mini Tutorial 2👩‍⚕️
ESR1 mutations are present in:
~4% of 1L setting
~30% in 2L+ setting
👉Not all ESR1 mutations are created the same!
-ESR1 Y537S is associated with relative resistance to fulvestrant!

pmc.ncbi.nlm.nih.gov/articles/PMC...

2 3 4

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

10/20 #TumorBoardTuesday
👩‍⚕️Mini Tutorial 1👩‍⚕️
Therapy options after progression on 1L ET+CDK4/6i are biomarker driven.
@dr-rshatsky.bsky.social

2 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

10/20 #TumorBoardTuesday
What would you select as next line of therapy?
1. Abemaciclib+fulvestrant
2. Elacestrant
3. Evaluate for clinical trials involving novel SERDs
@dr-rshatsky.bsky.social

1 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

9/20 #TumorBoardTuesday
⭐Case 2⭐
50 y/o postmenopausal F with de novo metastatic invasive ductal carcinoma, ER >95%, PR >95%, HER2– (IHC2+) involving the 🦴 and liver (intact function), progressed on 1st line ribociclib+AI after 12 months, w/ ESR1 Y537S mutation on ctDNA🤔
@dr-rshatsky.bsky.social

2 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

8/20 #TumorBoardTuesday
⚖️ efficacy with safety…
Inavo arm: ↑AEs vs control
All-grade hyperglycemia: 58.6%; grade 3 or 4: 5.6%
All-grade stomatitis: 51.2%; grade 3 or 4: 5.6%
All-grade diarrhea: 48.1%; grade 3 or 4: 3.7%
1° ppx for above was not offered in the trial
@dr-rshatsky.bsky.social

2 4 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

7/20 #TumorBoardTuesday
Back to our case🔎
Pt started inavo, palbo, and fulv
2 weeks in, developed grade 2 stomatitis self-dced inavo and palbo
Started dexamethasone+mucositis mouthwash, but sxs not resolved
Currently undergoing evaluation for subsequent therapy
@dr-rshatsky.bsky.social

a small yellow duck is laying on a table next to a notebook and the word no .

ALT: a small yellow duck is laying on a table next to a notebook and the word no .

media.tenor.com

4 3 5

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

6/20 #TumorBoardTuesday
👩‍⚕️Mini Tutorial 3👩‍⚕️
Pts R 1:1 to Inavo vs placebo +palbo+fulv
🔑findings:
Median f/u: 21.3 mon
Median PFS: 15.0 mon(Inavo) vs 7.3 mon (control) (HR 0.43; p<0.0001)
ORR: 58.4% (Inavo) vs 25% (control)
Consistent benefit across key subgroups
@dr-rshatsky.bsky.social

3 4 6

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

5/20 #TumorBoardTuesday
👩‍⚕️Mini Tutorial 2👩‍⚕️
Pt characteristics in INAVO120:
No prior treatment for ABC
PIK3CA mut
a1c≤6.0, fasting BG<126
~Half with ≥3 involved organ sites
~Half with liver involvement, ~40% with 🫁 involvement
~1/3 with 1° endocrine resistance, 2/3 with 2°
@dr-rshatsky.bsky.social

2 4 6

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

4/20 #TumorBoardTuesday
👩‍⚕️Mini Tutorial 1👩‍⚕️
Oct 2024, FDA approved inavolisib, palbociclib, and fulvestrant in endocrine resistant HR+/HER2- advanced breast cancer, based on the phase 3, INAVO120 study
@dr-rshatsky.bsky.social

3 3 6

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

3/20 #TumorBoardTuesday
Tissue NGS was not performed. CtDNA 🧬analysis revealing the following:
-PIK3CA H1047R

How does this impact your answer to the prior poll? 🤔
@dr-rshatsky.bsky.social

1 1 1

Xiaojie (Zoe) Zhang @zoezhang.bsky.social · Jan 15

3/20 #TumorBoardTuesday
Tissue NGS was not performed. CtDNA 🧬analysis revealing the following:
-PIK3CA H1047R

How does this impact your answer to the prior poll? 🤔
@dr-rshatsky.bsky.social

2 3 4