Stefan Zilli

Medical Oncologist // GI Oncologist

[Nicholas Hornstein @GIMedOnc]

#ASCO26

This one is special.

This is the hottest paper of 2026 and potentially in the history of pancreatic cancer.

Let’s dive in.

RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer
Abstract LBA5 (soon!)
Presentation: May 31, 2026, 3:21-3:33 PM CDT

For decades, pancreatic cancer has been where good ideas go to die.

We have optimized chemotherapy. We have sequenced chemotherapy. We have celebrated modest gains.

But the central driver of PDAC has always been sitting there in plain sight:

RAS.

More than 90% of pancreatic cancers have oncogenic RAS mutations, and until recently, we had essentially nothing direct to do about it.

Daraxonrasib is an oral RAS(ON) multiselective inhibitor targeting the active GTP-bound state of mutant and wild-type RAS.

And in RASolute 302, it delivered.

Quick hits:

📌 Phase 3 international randomized trial 500 patients with previously treated mPDAC Daraxonrasib vs investigator’s choice chemotherapy

🧬 RAS G12 population
91.8% of patients had RAS G12 mutations

📈 OS in RAS G12 population
13.2 vs 6.6 months
HR 0.40
P<0.001

📈 OS in overall population
13.2 vs 6.7 months
HR 0.40
P<0.001

📊 PFS in RAS G12 population
7.3 vs 3.5 months
HR 0.45
P<0.001

📊 PFS in overall population
7.2 vs 3.6 months
HR 0.49
P<0.001

🔥 12-month OS
Overall population: 53.2% vs 17.3%

⚠️ Toxicity matters, but this was not just more efficacy for more toxicity
Grade ≥3 AEs: 61.8% vs 69.6%
TRAEs leading to discontinuation: 1.2% vs 11.2%

This is the kind of survival curve we almost never get to see in pancreatic cancer.

This validates RAS(ON) inhibition in the most RAS-addicted major cancer. It takes a target we have talked about for decades and turns it into a clinically meaningful survival benefit in a randomized phase 3 trial.

The next questions come fast: 1L combinations, maintenance, perioperative disease, sequencing, resistance, toxicity management, and whether this becomes a new backbone.

RAS is here, and it couldn’t have come sooner.

https://t.co/Y4WJRlRRTk

@TheGutonclab @UGrewalMD @TimothyJBrownMD @OncoAlert @Onco_Nexus @ASCO
@NazliDizman @LauraAlderMD @DVAraujoMD @DrBarbiOnc @LauraEsfeller @FunchainMD @YGaritaonaindia @DrSAHaddad @jgong15 @iandresmeraz @SakditadMD @RamilaShilpakar @RohitBanwar @lungoncdoc

[Dr Amol Akhade @SuyogCancer]

Daraxonrasib: monotherapy vs + chemo in 1L mPDAC 🚀
RAS-mutant mPDAC:
Comparison of monotherapy vs combination
🔹 Monotherapy (n=40; eval n=35)
• ORR 51% | DCR 97%
• 6-mo PFS 71%
• ctDNA clearance 57% (n=28)

🔹 + GnP (gemcitabine + nab-paclitaxel) (n=40; eval n=39)
• ORR 59% | DCR 92%
• 6-mo PFS 84%
• ctDNA clearance 61% (n=28)
👉 Signal: is chemo adding much to this drug ? 🤔 @GIcancerDoc @Erman_Akkus @MyriamChalabi @OncoAlert @MedwatchKate
#PancreaticCancer #AACR26

[NEJM @NEJM]

Neoadjuvant gemcitabine–oxaliplatin, lenvatinib, and anti–PD-1 antibody led to longer event-free survival than surgery alone in resectable high-risk intrahepatic cholangiocarcinoma, with mainly low-grade adverse events. Full phase 2–3 ZSAB-neoGOLP trial results: https://t.co/PpNO71uhur

[Arndt Vogel @ArndtVogel]

HERIZON-GEA-01 phs-3: Zanidatamab + CTx +/- Tislelizumab in 1st line Her2+ locally advanced unresectable or mG/GEJ adenocarcinoma
#ASCOGI26
👉 ORR: 70 vs 69 vs 65%
👉 mPFS: 12.4 vs 12.4 vs 8.1 mo
👉 mOS: 26.4 vs 24.4 vs 19.2 mo
👉Clinical benefit across PD-L1 subgroups
🧐 convincing data, new SOC?!
@myesmo @ASCO

[Oscar Tahuahua @OscarTahuahua]

@Nature Review. HCC remains a major challenge, ~900,000 cases/yr with mortality nearly the same

Curative options (resection, ablation & transplant) apply to only 10–20% of pts & recurrence reaches 70% at 5 yrs.

The field is moving toward biology-driven decision-making using biomarkers, PET, functional MRI, machine perfusion to ↑ transplant access & perioperative ICI to ↓ recurrence.

SBRT is increasingly used for downstaging & bridging
https://t.co/qIKp0y795J @OncoAlert

[OncoAlert @OncoAlert]

The OncoAlert #GICancer Faculty, led by Dr. Akkus🇹🇷 , Dr. Hornstein🇺🇸 , Dr. Balsa🇪🇸 , Dr. Cifuentes 🇨🇴 & Dr. Morgan🇺🇸 have selected the OncoAlert TOP 🔟 #ESMO25 Abstracts In #CRC , #HCC, #GEJC #ColonCancer to be presented in Berlin🇩🇪 Picked using a Delphi System to establish our picks.

✅ LBA10 :BEMARITUZUMAB PLUS CHEMOTHERAPY FOR ADVANCED OR METASTATIC FGFR2B OVEREXPRESSING GASTRIC OR GASTROESOPHAGEAL JUNCTION CANCER: FORTITUDE-101

✅2098M0
CADONILIMAB PLUS CHEMOTHERAPY VS. CHEMO AS FIRST-LINE TREATMENT FOR ADV.
GASTRIC OR GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA: COMPASSION-15

✅LBA50
IMBRAVE152/SKYSCRAPER-14: FIRST-LINE TIRAGOLUMAB + ATEZOLIZUMAB + BEVACIZUMAB VS PLACEBO + ATEZO + BEV IN UNTREATED LOCALLY ADVANCED OR METASTATIC HCC

✅LBA51
IKF-035/ABC-HCC: ATEZOLIZUMAB PLUS BEVACIZUMAB VS. TRANSARTERIAL CHEMOEMBOLIZATION IN INTERMEDIATE-STAGE HEPATOCELLULAR CARCINOMA

✅14700
PERIOPERATIVE CAMRELIZUMAB PLUS RIVOCERANIB IN RESECTABLE HCC (CARES-009)

✅LBA11
NEOADJUVANT TORIPALIMAB PLUS LENVATINIB AND GEMOX IN RESECTABLE, HIGH-RISK INTRAHEPATIC CHOLANGIOCARCINOMA

✅LBA30
ZANZALINTINIB PLUS ATEZOLIZUMAB VS REGORAFENIB IN PREVIOUSLY TREATED MET.
COLORECTAL CANCER: PRIMARY OS ANALYSIS FROM STELLAR-303 STUDY

✅BA9
CTDNA-GUIDED ADJUVANT CHEMOTHERAPY DE-ESCALATION IN STAGE III COLON CANCER: ANALYSIS OF THE CTDNA-NEGATIVE COHORT FROM THE RANDOMIZED AGITG DYNAMIC-I|I

✅LBA28
DESTINY-CRC02: TRASTUZUMAB DERUXTECAN (T-DXD) MONOTHERAPY (HER2+ MCRC)

✅LBA85
RESULTS OF A RANDOMIZED PHASE 3 TRIAL OF SHORT-COURSE VERSUS LONG-COURSE PREOPERATIVE CHEMOTHERAPY FOR STAGE I-III PANCREATIC DUCTAL ADENOCARCINOMA

#OncoAlertAF
@nataliagandur @acampsmalea @BRicciutiMD
@yekeduz_emre @HHorinouchi @FadiHaddad_MD
@Abdallah81MD @FernandoOnco
@ElisaAgostinett @to_be_elizabeth @bavilima @realbowtiedoc @Erman_Akkus @Lucarecco @GaiaGriguolo @JankovicK
@MarioBalsaMD @DrMirallas @GIMedOnc @OscarTahuahua @UOzkerim @DrRishabhOnco @Onco_Cifu88

OncoAlert GI faculty
@pashtoonkasi @CathyEngMD @marklewismd @manjuggm @stacy_hurt @ARosen380 @KoheiShitara @GillSharlene @BenWestphalen

#gicancer
#gastrointestinalcancer
#colorectalcancer
#colorectalcancerawareness
#coloncancer
#stomachcancer
#livercancer
#esophagealcancer
#pancreaticcancer

[Dr Amol Akhade @SuyogCancer]

🚨 New Molecules to Watch at #ESMO25 (GI Cancers)
🔹 KRAS G12D inhibitors (GFH375, HRS-4642, INCB161734)
🔹 Zanzalintinib + Atezolizumab (STELLAR-303, mCRC)
🔹 Sirexatamab (DKN-01, MSS mCRC)
🔹 RC118 (CLDN18.2 ADC, Gastric/GEJ)
🔹 Telisotuzumab Adizutecan (c-MET ADC)
🔹 Nofazinlimab + Lenvatinib (HCC)
🔹 Tiragolumab + Atezo+Bev (HCC)
🔹 Bemarituzumab + Chemo (FGFR2b+, Gastric/GEJ)
Precision oncology pipeline heating up 🔥 @myESMO

[Mario Balsa @MarioBalsaMD]

💥 It’s here! The new ESMO Clinical Practice Guidelines for localized rectal cancer (@Annals_Oncology)
🔗 https://t.co/cdCezBb6G7

📌 Covers:
•Imaging & diagnosis
•Staging & risk assessment
•Treatment & follow-up
•Algorithms for local & LA disease

When it comes to rectal cancer, guidance just got…straight to the point 🎯

@OncoAlert #OncoAlertAF @OncoReporte @myESMO @seom @GrupoTTD

[Arndt Vogel @ArndtVogel]

🔥off the press, now fully published
Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
@Annals_Oncology
https://t.co/Ip3o0ija5C
😅all you need to know!
@myESMO

[Mario Balsa @MarioBalsaMD]

💥 RATIONALE-306 at #ESMOGI25: Tislelizumab + chemo improves OS vs placebo + chemo in LA #ESCC

🎯mOS: 25.6 vs 12.3m | HR 0.49
🎯mPFS: 9.7 vs 6.9m | HR 0.56
🎯ORR 61% vs 39% | DoR 22.1 vs 5.7m

For LA ESCC, tislelizumab adds reason to the rationale. 🔍
#OncoAlert @OncoAlert @myESMO @_SEOM @GrupoTTD

[Dr Amol Akhade @SuyogCancer]

🔬 CRC Screening Face-Off: Stool 🧻 vs Blood 🩸
Not all non-invasive tests are created equal.
Let’s break it down 👇
🧪 CRC Sensitivity
✅ Cologuard Plus: 95%
✅ ColoSense: 94%
🩸 Shield (blood): 80–83%
⚪ FIT: 67–91%
⚠️ Advanced Adenoma Detection (PREVENTION!)
✅ ColoSense: 46%
✅ Cologuard: 43%
⚪ FIT: 20–30%
🩸 Shield: ❌ 13–16%
💥 High-Grade Dysplasia
✅ Cologuard: 74%
⚪ FIT: 47%
🩸 Shield: ❌ 23%
🧬 ColoSense: NA
🎯 Specificity
FIT: 95% | Shield: 90% | Cologuard: 91–94% | ColoSense: 88%
🧵 Verdict: Blood-based cfDNA is convenient but underperforms where it matters—early detection of pre-cancer.
Cologuard & ColoSense are clear leaders in prevention.
If we want to prevent, not just detect, CRC—🧻 still beats 🩸.
#OncologyX #CRCscreening #ESMOGI2025 @myESMO

[Oscar Tahuahua @OscarTahuahua]

Advances in Molecular Pathology &amp; Therapy of NSCLC

🌟Precision oncology is no longer optional. This review maps the molecular landscape of NSCLC (EGFR, ALK, KRAS, etc.), resistance, spatial omics &amp; AI, and shows how biology is reshaping lung cancer treatment. 1/2
@OncoAlert

[Kohei shitara @KoheiShitara]

Pleased to report FGFR2b expression in gastric cancer and relationship with other biomarkers @ESMO_Open @myESMO. The results of bemarituzumab phase 3 studies are awaited.@OncoAlert @oncodaily
https://t.co/wmaLAJPq8q

[Krishan Jethwa @KrishanJethwa]

🚨SPRING-01🚨

🔍Locally Advanced Rectal Cancer

RCT:
25 Gy x 5 ➡️ CAPOX +- Sintilimab

🔥+ Sintilimab demonstrated:

✅⬆️pCR 59% vs 33%
✅No significant adverse surgical or safety signals

Time to explore with organ preserving approaches⁉️

#ASCO25

[Krishan Jethwa @KrishanJethwa]

🚨PANOVA-3🚨

Locally advanced PDAC
🔍 Gem + nab-Paclitaxel +/- Tumor Treating Fields (TTF)⚡️

🔥TTF Demonstrates:
✅⬆️OS
✅⬆️Distant-Met Free Survival
✅⬆️Pain-Free Survival
✅⬆️QoL

🧐A new SoC option for patients with LAPC. While no improvement in local control seem, perhaps TTF combined with local radiotherapy may move the needle even further!

Simultaneous pub here: https://t.co/bvyYNi871S

#ASCO25

[Lizzy Smyth @LizzySmyth1]

#ASCO25
Checkmate 577 final OS
➡️ No significant OS benefit overall for adjuvant nivo
SCC maybe....0.72
Adeno no .. HR 0.92
Post ESOPEC another reason to avoid CRT in adenocarcinoma
👀 MATTERHORN tomorrow folks!

[Nicholas Hornstein @GIMedOnc]

#ASCO25

DESTINY-Gastric04 sets a new 2L standard for HER2+ gastric/GEJ cancer.
T-DXd vs Ramucirumab/Paclitaxel in post-trastuzumab GEJ/gastric AC (N=494):

🧬 OS: 14.7 vs 11.4 mo (HR 0.70, p=0.004)
📉 PFS: 6.7 vs 5.6 mo
🎯 ORR: 44% vs 29%

Some minor concerns:
⚠️ ILD/pneumonitis in ~14% (mostly grade 1–2)
↩️ Only 26% of control arm got T-DXd post-progression
🔬 HER2 heterogeneity ?
📊 Subgroup CI >1.0 in many cohorts
🌍 Open-label + regional variability

Regardless, this establishes T-DXd as the preferred 2L option—if HER2 remains positive.
Gastric follows in the footsteps of breast, where pathologic confirmation of HER2 status at time of progression is now critical.

@ASCO @larvol @oncoalert @oncbrothers
🎙️ Featured Voices:
@yekeduz_emre @DRBakaloudiMD @AndreaAnampaG @ReginaBarCar @cwspeers
@FunchainMD @MKnoll_MD @bavilima @KrishanJethwa @cancerassassin1
@ReneeSaliby @MikeSerzanMD @OncBrothers @coloncancergal @ShannonWestin
@SuyogCancer @supriyadocc @UGrewalMD @coffeemommy @RyanNipp
@realbowtiedoc @crisbergerot

[Arndt Vogel @ArndtVogel]

Perioperative systemic therapy for resectable colorectal peritoneal metastases
#ASCO25
🔎 CAIRO-6 phs 3 trial
👉mPFS 14 vs 7 mo
👉mDFs 12 vs 7 mo
👉mOS 44 vs 39 mo
🧐 No OS benefit in IIT, but better OS in synchronous right-sided tumors
@myESMO

[Arndt Vogel @ArndtVogel]

NIVO plus IPI vs CTx or NIVO for MSI-H/dMMR mCRC:
#ASCO25
🔎Expanded analyses from CheckMate 8HW
👉ORR N/I vs N71 vs 58%
👉mPFS N/I vs CTx nr vs 30.8 mo
👉mPFS N/I vs N 54 vs 5.9 mo
🧐 Highly effective treatment, acceptable toxicity, supports N/I as SOC
@myESMO

[Nicholas Hornstein @GIMedOnc]

#ASCO2025
🚨 BREAKWATER OS data lands—and it must redefine 1L standard of care in BRAF V600E-mutant mCRC.

EC + mFOLFOX6 vs SOC (chemo ± bevacizumab):
📊 PFS: 12.8 vs 7.1 mo (HR 0.53, p < 0.0001)
🧬 OS: 30.3 vs 15.1 mo (HR 0.49, p < 0.0001)
✅ Dual primary endpoints met
🛡️ Manageable safety profile

Prior ORR data drove accelerated approval—
This confirms it: EC + chemo is the new SOC.
https://t.co/1EhAIjviPp

Congratulations to @skopetz and team!!

@ASCO @larvol @oncoalert
🎙️ Featured Voices: @yekeduz_emre @DRBakaloudiMD @AndreaAnampaG @ReginaBarCar @cwspeers @FunchainMD @MKnoll_MD @bavilima @KrishanJethwa @cancerassassin1 @ReneeSaliby @MikeSerzanMD @OncBrothers @coloncancergal @ShannonWestin @SuyogCancer @supriyadocc @UGrewalMD @coffeemommy @RyanNipp @realbowtiedoc @crisbergerot