Michael Shusterman, MD

Gastrointestinal Medical Oncologist. Tweets my own. #Meded

[Michael Shusterman, MD @guildsman]

GI Oncology standard regimen doses remain too high for many real world patients. Retrospective and prospective trials demonstrating benefit of reduced doses or dose escalation are accumulating. #meded #gionc #crcsm #pancsm

[Nicholas Hornstein @GIMedOnc]

I thought #ESMO26 was the year of IO and this CART just came out of nowhere to smash expectations
🤯
Is this real?

SL-28 (1002O): off-the-shelf allogeneic leukocytes from healthy donors. No genetic modification, no HLA matching, no conditioning. 12 heavily pretreated patients.

• ORR 66.7% (4 CR, 4 PR)
• 4 SD, 0 PD
• mDoR not reached in responders
• mPFS 24.7 mo

• 4 of 12 patients died, all labeled non-cancer related. In a cell therapy dataset I need to know what killed them.

• The 12 mix a Phase 1/2 that started in 2026 with expanded-access patients. A 24.7 mo median PFS likely utilizes the compassionate-use cases.

• SL-28 runs on "TezR" receptors, a system first described by the company's founders (one of whom presented today). I'd love to see someone else replicate it.

Have we finally entered the era of solid tumor CAR-Ts?

@OncoAlert @TheGutOncLab
@Onco_Nexus

[Michael Shusterman, MD @guildsman]

Helpful Duffy Null ranges for individuals. Not sure how we will set chemotherapy guidelines without either a pragmatic clinical trials or very large real world database analyses (so many potential confounders there).

[J Mark Sloan @Jmarksloan]

We now have Duffy-null reference ranges for adults and children.

Next step-
understand and accomodate Duffy null status when considering eligibility for clinical trial inclusion, medications (eg azathioprine) or dose reductions (eg for chemo)

https://t.co/1r6JBZ6FYu

[Michael Shusterman, MD @guildsman]

@KRASKickers Submitted! What a fantastic effort to support a most excellent group!

[KRAS Kickers @KRASKickers]

This month, Revolution Medicines will donate $50 to @KRASKickers for every message of support submitted for up to $30,000.

Plant a seed of hope. Share your message:

LINK:
"Share a few words of encouragement for people impacted by RAS-addicted cancers. Your message will be collected as part of this shared expression of hope."

https://t.co/zq8qZfZvto

Thank you to @RevMedicines !

[Nicholas Hornstein @GIMedOnc]

Anyone impacted or working with GI cancer patients should take a moment and offer some words of support to patients battling the disease. KRAS Kickers has been an awesome resource over the years and RevMed is providing significant funding to them (if people click a link and submit a few anonymous words).

@TheGutOncLab @Onco_Nexus @OncoAlert

[BackTable Tumor Board @_backtableONC]

Can circulating tumor DNA flag a pancreatic cancer recurrence before the scan does, and if it rises, should treatment start?

Drs. Arsen Osipov (@DrArsenOsipov) , Daniel Ahn, and Andrew Hendifar (@DrHendifar) on neoadjuvant chemotherapy, pathologic response, prehabilitation, adjuvant RAS inhibitors, and ctDNA.

Watch the full episode on the BackTable App:
https://t.co/rp8e216aTC

#ONC89 #PancreaticCancer #GIOncology #KRAS #CreatorWeekend @MayoClinic @CedarsSinai @ASCO @NCCN

[Michael Shusterman, MD @guildsman]

Looking forward and honored to join @MSKCancerCenter and the GI Oncology group under fantastic leadership of @YJanjigianMD!

[Yelena Y. Janjigian MD @YJanjigianMD]

Welcome to the GI Oncology family at @MSKCancerCenter, Michael! I was immediately impressed by your clinical insight, thoughtfulness, and passion for advancing cancer care. Thrilled to have you join us and excited for all we will accomplish together! @guildsman

[KRAS Kickers @KRASKickers]

RASonate 312

@RevMedicines press release

"The company is initiating a global, randomized Phase 3 trial, RASonate 312, evaluating the combination of zoldonrasib, cetuximab and FOLFOX/FOLFIRI in patients with treatment- naïve metastatic RAS G12D CRC compared with standard of care.

The trial is based on strong initial clinical activity observed with the zoldonrasib combination regimen, including encouraging objective response rates and disease control rates, along with an acceptable safety and tolerability profile generally consistent with what would be expected for cetuximab and FOLFOX."

https://t.co/QsxuWJsEzF

[Michael Shusterman, MD @guildsman]

Excited to announce the next step in my journey: I am joining the Solid Tumor GI Oncology Service @MSKCancerCenter! Deeply grateful to my colleagues, mentors, and fellows @Perlmutter_CC! Eager to dive into exceptional trials, clinical care, research, and education @MSKCC!

[Nicholas Hornstein @GIMedOnc]

Would you like a glimpse of the future? Where solid tumor oncology may be heading?

Look no further.

Agenus may have had some ups and downs in the past (BATMAN -> ROBBIN), but Bot Bal looks like it has the capacity to absolutely change how we manage MSS solid tumors.

UNICORN, now in Nature Medicine. Phase 2, non-randomized, window-of-opportunity. Resectable rT3-4 colon cancer. One dose of botensilimab, two doses of balstilimab, surgery around day 30-40.

Highlights:

MPR 36% (5/14) in MSS disease, pCR 29%. Omg. (compare to FOLFOX in FOxTROT: 8%)
Bot alone in MSS: 0%. The PD-1 matters.
dMMR Bot Bal: MPR 100%, pCR 93%
😍12-month EFS 100% in both Bot Bal cohorts

Yes there is tox. irAEs in 54%, mostly flu-like symptoms, and only one grade 3 (hyperthyroidism). No grade 3 diarrhea.

Every MSS responder cleared ctDNA before surgery, that’s a helpful tool for predicting response in a disease that may fibrose and stay visible on imaging.

The holy grail is almost here: melting the majority of rectal cancers away. In MSI-H we have AZUR-1. In MSS, perhaps we have this in the future.
https://t.co/5x2tbpDNDm
@OncoAlert @TheGutOncLab @Onco_Nexus

[Oncology Brothers @OncBrothers]

3. CLARITY-Gastric01: PhIII Sonesitatug vedotin (CLDN18.2 ADC) vs Chemo in 2L+ CLDN18.2+ Gastric/GEJ

- 3L+ mOS 10.0 vs 5.0mos (HR 0.47)
- 2L+ mOS 10.6 vs 6.4 mos (HR 0.58)
- PFS not significant 🤔
- ADC activity even at lower CLDN18.2 expression

4/5

[Oncology Brothers @OncBrothers]

4. HARMONi-GI1: PhIII, Ivonescimab + gem/cis vs durva + gem/cis in 1L advanced BTC (n=682 🇨🇳 only study):

- mOS 14.9 vs 12.1mos (HR 0.75)
- mPFS 8.4 vs 5.8mos (HR 0.61)
- ORR 54% vs 33%
*Global confirmation needed… but we’ll likely see Ivo/PD1-VEGFi in our practice soon*

5/5

[Michael Chuong @MikeChuongMD]

In this @OncJournal commentary, @EileenMOReilly and I highlight emerging preclinical evidence of synergy between RAS inhibition and RT in PDAC and make the case for prospective clinical trials evaluating this combination across the disease spectrum

https://t.co/rIsQI4I08e

[Thor Halfdanarson @OncoThor]

Now that I am mostly recovered from ESMO (and my dual flu/COVID shot yesterday), I am diuresing on NET papers I never got around to post...

Here is a super practical review on the pitfalls of SSTR PET imaging, false positives etc. Everyone who orders SSTR PETs needs to know about that...

I love me some practical review papers on a Saturday morning...

https://t.co/miAfNMnF0v

[KRAS Kickers @KRASKickers]

Guess whose slide deck from #AACR26 is online?

slide 23 - BI-2493

https://t.co/pEts54Mjjb

[Nicholas Hornstein @GIMedOnc]

GI Oncology saw some major changes in NCCN this week. 🔥

🧬 1. Daraxonrasib is officially in the pancreatic cancer guidelines

You knew it was coming, now it is here. Preferred, Category 1. Use it.

RASolute-302 in previously treated metastatic PDAC:
OS: 13.2 vs 6.6 months, HR 0.40
PFS: 7.3 vs 3.5 months, HR 0.45

Subsequent therapy, and importantly it also sneaks into 1L as “useful in certain circumstances,” although only 2B for fit patients (but still there, YAY).

So no, we are not throwing FOLFIRINOX/NALIRIFOX in the garbage (yet).
But a RAS inhibitor is now a standard treatment for pancreatic cancer.

🔵 2. Zanidatamab + tislelizumab in NCCN for HER2+ GEA
Zanidatamab + tislelizumab + chemo vs trastuzumab + chemo:
PFS: 12.4 vs 8.1 months, HR 0.63
OS: 26.4 vs 19.2 months, HR 0.72

NCCN now lists zanidatamab-based therapy as Preferred first-line treatment.

But… Category 2A.

Why? 2A still means uniform NCCN panel consensus (≥85%) that the treatment is appropriate (so yes, you should be using this for these patients), but officially reflects lower-level evidence than Category 1.
Except HERIZON was a randomized phase III trial with positive outcomes.

So why 2A?
Two informed guesses.

1. No US patients were enrolled. It was a large international study, and frankly the incredibly diverse patients I see in NYC probably look more like a global trial population than many historical US trials.

2. The control arm didn't include PD-1.
HERIZON compared against trastuzumab + chemo, while our current US standard for PD-L1 CPS ≥1 is pembrolizumab + trastuzumab + chemo.

But before we poo-poo HERIZON because of the comparator, let's look at what those studies actually achieved.

KEYNOTE-811, CPS ≥1:
PFS 10.9 months
OS 20.1 months

HERIZON:
PFS 12.4 months
OS 26.4 months

Of course, no one would ever compared across trials. 😅
But HERIZON's own trastuzumab/chemo control arm had an OS of 19.2 months. This wasn't a control arm falling over.

To me, these data show a real advance in HER2 therapy.
If you’re using it, do watch for the diarrhea.

NCCN specifically recommends antidiarrheal prophylaxis with zanidatamab and avoiding bolus 5-FU. Grade ≥3 diarrhea was 24.8% with the quadruplet but can be controlled and is only during the first few treatments.

3. And very briefly, MATTERHORN
FLOT + durvalumab was upgraded 2B → 2A for PD-L1 <1 and diffuse-type EGJ adenocarcinoma.
Overall MATTERHORN: 2-year EFS 67.4% vs 58.5%, HR 0.71, with pCR 19.2% vs 7.2%.

Love seeing forward progress in GI Oncology.

@TheGutOncLab @OncoAlert @Onco_Nexus @oncodaily

[Arndt Vogel @ArndtVogel]

ACTICCA-1 trial: Adj. GemCis vs standard of care after curative intent resection of BTC
#ESMO26 #ESMOAmbassadors
👉 DFS at 2yrs: 52 vs 44%
👉mDFS: 23.3 vs 20.6
👉 mOS: 58 vs 48 mo
👉expected toxicity for the doublet
🧐 Trend for OS benefit, not an option for all, but may be considered as option for selected pts
@myESMO @ASCO

[Nieves Martinez Lago MD PhD @DraMartinezLago]

#ESMO26 🧬 ACTICCA-1 | Phase III

👥 Resected BTC | Adjuvant setting
💊 GemCis vs standard of care

📈 2-y DFS: 52% vs 44%
⏳ mDFS: 23.3 vs 20.6 mo
🎯 mOS: 58 vs 48 mo

⚠️ Expected toxicity with GemCis

💡 Trend towards OS benefit, but not a new standard.

@OncoAlert

[Arndt Vogel @ArndtVogel]

🔥Presidential session at ESMO 2026 🔥
HARMONi-GI1 ph-3: Ivonescimab + CTx vs durvalumab + CTx as 1L for BTC
#ESMO26 #ESMOAmbassadors
👉ORR: 53.8 vs. 32.5 %
👉mPFS: 8.4 vs 5.8 mo
👉mOS: 14.9 vs. 12.1 mo
🧐 Very promising Chinese data, would be great to see data in a global population
@myESMO @ASCO

[Allan Pereira, MD, PhD @DrAllanPereira]

🧑‍🔬I recently posted data from G-HOPE-001 and CLARITY-Gastric01, two phase 3 trials evaluating their respective ADCs in previously treated CLDN18.2-positive gastric, GEJ, or esophageal adenocarcinoma.

🧐 Can you spot the differences between arcotatug tavatecan and sonesitatug vedotin?

Btw, pay attention to the interesting design trade-off between retaining versus silencing the antibody’s Fc region.

😲Non-Fc-silenced ADCs (sonesitatug vedotin): Because ADCC and CDC provide an additional mechanism of tumor-cell killing, this ADCs may retain activity even in tumors with lower levels of CLDN18.2 expression.
- Trade-off: Preserving Fc activity may also increase the potential for immune-mediated toxicity, particularly because normal gastric mucosa expresses CLDN18.2.

🤐Fc-silenced ADCs (arcotatug tavatecan): Without additional ADCC/CDC-mediated killing, the ADC depends more heavily on target binding, internalization, and intracellular payload release. As a result, higher levels of CLDN18.2 expression may be needed to achieve sufficient payload delivery and tumor-cell killing.
---
-ADC (Antibody-Drug Conjugate)
-ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity)
-CDC (Complement-Dependent Cytotoxicity)
-Fc (Fragment Crystallizable region)
-ILD (Interstitial Lung Disease)

#GastricCancer #CLDN182 #ESMO26 #GIOnc