“New Standard of Care”? Lung Cancer KOLs on KRASCENDO-1 and ESMO26

This post collects physician reactions on X to the lung cancer data at ESMO26. It covers four areas: KRAS G12C (KRASCENDO-1), first-line immunotherapy in PD-L1 ≥50% NSCLC (PERSEE), small cell lung cancer (DeLLphi-305) and EGFR-mutant NSCLC after TKI (SAFFRON, OptiTROP-Lung04, PANKU-Lung01, HERON-Lung01). SARON and OptiTROP-Lung06 are under Also discussed.

Lung physicians called PERSEE and DeLLphi-305 practice changing. Two called divarasib a new standard of care for KRAS G12C after KRASCENDO-1. Four China-only ADC trials drew split reactions. Divarasib, first-line tarlatamab + durvalumab and the ADCs are not FDA-approved.

On October 25, Narjust Florez, MD, wrote: "Cautiously optimistic, as most control patients received sotorasib." The same day, Stephen V Liu, MD, wrote that discussant Benjamin Besse "Rightly points out lack of crossover in a study with a PFS endpoint as unjust." On October 26, Tom Newsom-Davis wrote: "A new standard of care arrives in advanced KRAS G12C NSCLC: Divarasib (Krascendo-1)."

1. KRAS G12C: KRASCENDO-1

Divarasib vs sotorasib or adagrasib in KRAS G12C NSCLC. Primary PFS 9.8 vs 5.7 mo, HR 0.58. OS (key secondary) 17.7 vs 12.0 mo, HR 0.56 (LBA5, ESMO26; DCO 19-May-2026). Divarasib is investigational.

Tom Newsom-Davis on KRASCENDO-1:

A new standard of care arrives in advanced KRAS G12C NSCLC: Divarasib (Krascendo-1)

🔸 Global, randomised, phase 3
🔸 Compared to current KRASi (mainly sotorasib)
🔺 No cross-over

What do we know so far?
🔹 2L sotorasib or adagrasib show modest PFS benefit vs docetaxel, but no OS benefit

What did we see at #ESMO26?
✅ Improved PFS, 9.8 v 4.7m: HR 0.58
✅ Improved ORR, 58% v 32%
✅ Improved OS, 17.7m v 12m: HR 0.56
⚠️ Lower Gr3+ AEs, but more Gr1-2 AEs - especially GI

What does this mean?
❗️New standard of care for KRAS G12C
✅ Clearly superior to current options
🤔 Need QoL & PRO data
🤔 Need intra-cranial activity data
⚠️ Side effects remain an issue, albeit lower grade (Gr2 diarrhoea is still pretty miserable)
❗️Drug access will be the main issue, especially with Sotorasib withdrawal of funding in many countries
🤔 1L, in combination with other agents, likely to be ultimate place for this drug

#LCSM

— Tom Newsom-Davis (@tnewsomdavis) Oct 26, 2026

Context: his post lists control-arm PFS as 4.7 mo; LBA5 reports 5.7 mo.

Narjust Florez, MD, FASCO, on KRASCENDO-1:

Not all KRAS G12C inhibitors are equal. Once approved, divarasib could be our preferred option after first line, and the real question is how quickly we move it to the first line.

Cautiously optimistic, as most control patients received sotorasib.

#ESMO26 #lcsm #KRAS https://t.co/ku1dkDjieA

— Narjust Florez, MD, FASCO (@NarjustFlorezMD) Oct 25, 2026

Stephen V Liu, MD, on Benjamin Besse's discussion:

Brilliant discussion from Dr. @BenjaminBesseMD at #ESMO26 on the Krascendo 1 study of divarasib vs sotorasib/adagrasib. Rightly points out lack of crossover in a study with a PFS endpoint as unjust. Excellent points all around. #ESMOAmbassadors https://t.co/AZp29NMYLI

— Stephen V Liu, MD (@StephenVLiu) Oct 25, 2026

Also posting on KRASCENDO-1: Clive Peedell.

2. First-line IO in PD-L1 ≥50%: PERSEE

Pembrolizumab + chemotherapy vs pembrolizumab alone, first-line advanced NSCLC with PD-L1 ≥50%. PFS 16.1 vs 6.9 mo, HR 0.56. OS 50.2 vs 29.9 mo, HR 0.77; not powered for OS and not significant (2614O, ESMO26; DCO 7-Apr-2026). Grade ≥3 TRAEs 54% vs 19%. Both regimens are already FDA-approved.

Tom Newsom-Davis on PERSEE:

Another practice changing result for lung oncology at #ESMO26: PERSEE trial

👉 Academic 🇫🇷 multicentre study
👉 Which is best in 1L PD-L1 >50% NSCLC: pembro (P) or chemo+pembro (CT-P)?

What do we know already?
🔹Retrospective study suggested modest benefit of CT-P

What did this study do?
🔸 Phase 3, multi-centre, randomised
🔸 Local PD-L1 testing
🔸 1:1 P or CT-P
🔸 1’ end-point = PFS

What was found? CT-P…
✅ Improved mPFS in whole popn (HR 0.56)
✅ Improvement was in all PD-L1 levels (50-74; 75-90; 90-100%)
✅ Improvement in mOS (HR 0.77), not powered for significance
✅ Increased ORR: 77% v 50%
✅ Reduced early progression

Thoughts:
🤔 An easy way to improve the outcome for most of your PD-L1 >50% pts: add chemo to the pembro
🤔 CT-P still not for everyone: less/no benefit in >70yrs, and squamous histology
🤔 Shame PS=2 not included, to make this more real-world
🤔 Had not expected CT-P to be better across all PD-L1 levels
🤔 Pembro only still has a role in select PD-L1 high, especially >90% with KRAS G12C

Will this change my practice?
👉 I already use CT-P in PD-L1 50-80%, but I will now use it in >80% for most (but not all) pts

👏 Great study. Congratulations to authors #LCSM

— Tom Newsom-Davis (@tnewsomdavis) Oct 25, 2026

Gilberto Lopes on PERSEE:

PERSEE at #ESMO26: PD-L1 ≥50% advanced NSCLC.

Pembrolizumab + chemo vs pembrolizumab alone:

PFS: 16.1 vs 6.9 mo (HR 0.56)
OS: 50.2 vs 29.9 mo (HR 0.77; not statistically significant)
Grade ≥3 TRAEs: 54% vs 19%

Better disease control, more toxicity. Individualize.

#LungCancer

— gilberto lopes (@GlopesMd) Oct 27, 2026

Also posting on PERSEE: Julien Mazieres, Estela Rodriguez and Clive Peedell.

3. Small cell lung cancer: DeLLphi-305

Tarlatamab + durvalumab vs durvalumab, first-line maintenance in ES-SCLC. OS 21.1 vs 12.7 mo, HR 0.42 (LBA3, ESMO26 / NEJM; interim, DCO 7-Jul-2026). The first-line combination is investigational. Tarlatamab is FDA-approved 2L+.

Narjust Florez, MD, FASCO, on DeLLphi-305:

In extensive-stage small-cell lung cancer, many of our patients never make it to second-line therapy.

Adding tarlatamab to durvalumab in first-line maintenance gives them our most active agent while they can still benefit. 80% were alive one year after starting maintenance, including patients with brain and liver metastases.

CRS was mostly limited to the first two doses, with no serious neurologic events.

Small steps in SCLC, but this one matters for our patients. 💙
#ESMO26

— Narjust Florez, MD, FASCO (@NarjustFlorezMD) Oct 26, 2026

Christine Lovly, MD, PhD, FASCO, on DeLLphi-305:

Median OS almost 2 years in ES-SCLC with Tarlatamab+Durvalumab maintenance = practice changing!
➡️ Challenge remains implementing Tarlatamab broadly + equitably so that all patients with ES-SCLC may benefit from this revolutionary therapy.
@OncoAlert #ESMO26 @NEJM https://t.co/Ug6TxnAd1J

— Christine Lovly, MD, PhD, FASCO (@christine_lovly) Oct 24, 2026

Julien Mazieres on DeLLphi-305:

Tarlatamab + durva significantly improve OS, PFS, and ORR in 1LM ES-SCLC in maintenance setting. Maintenance vs 2L tarlatamab will be discussed and we wait for data in frontline. Anyway DLL3 drugs are definitely changing thepronostic of SCLC. @OncoAlert @myESMO #ESMO26 https://t.co/Pnab4DlYFd

— Julien Mazieres (@JulienMazieres) Oct 24, 2026

Also posting on DeLLphi-305: Clive Peedell.

4. EGFR after TKI: SAFFRON, OptiTROP-Lung04, PANKU-Lung01, HERON-Lung01

Four phase 3 trials in EGFR-mutant NSCLC after TKI. Three tested different ADCs: sac-TMT (TROP2), iza-bren (EGFR×HER3 bispecific) and ruzaltatug rezetecan (HER3). OptiTROP-Lung04, PANKU-Lung01 and HERON-Lung01 were China-only. None of the ADCs is FDA-approved. Sac-TMT is approved in China after EGFR TKI.

Tom Newsom-Davis on all four trials:

A lot of new data on 2L post-EGFR TKI NSCLC treatment options in #ESMO26. What can we make of it all?

OptiTROP-Lung04:
👉 Sacituzumab-TMT (TROP2 ADC) vs. chemo
🔹 China-only, Ph3, randomised, open-label
✅ Previously positive PFS (ESMO 2025)
✅ Improved OS, 25.9 v 17.4m: HR 0.69
⚠️ Similar TRAEs, slightly more Gr1-2 with Saci-TMT

SAFFRON:
👉 Adding Savolitinib to Osimertinib in MET over-expressing (OE) / amplified
🔹 Global, Ph3, randomised v chemo
✅ Improves mPFS 7.6m v 5.4m: HR 0.55
✅ Similar benefit for OE & amplified pts
✅ Improved OS 17.8m v 12.9m: HR 0.68
⚠️ Lower Gr3+ AEs (40% v 52%) but higher Gr1-2 toxicity - oedema as expected

PANKU-Lung01:
👉 Iza-Bren (EGFR x HER3 ADC) v chemo
🔹 China-only, Ph3, randomised
✅ Improved mPFS 11.7 v 5.7m: HR 0.40
✅ Improved ORR 60% v 34%
❓OS, immature
⚠️ Higher Gr3+ AEs (78% v 62%). Mainly myelosupression
⚠️ High dose interruption (53%) & reduction (60%)
⚠️ Needs GCSF prophylaxis

HERON-Lung01:
👉 Rus-Rez (HER3 ADC) v chemo
🔹 China-only, Ph3, randomised
✅ Improves mPFS, 8.3m v 5.4m: HR 0.47
❓OS, immature
⚠️ Similar Gr3+ TRAEs, but higher Gr-2 AEs. Mainly myelosupression

…and add to this current / other options:
🔸 Pemetrexed & carboplatin
🔸 COMPEL: Osimertinib + chemo
🔸 MARIPOSA-2: Amivantamab + chemo
🔸 HARMONi: Ivonescimab + chemo

🤯

So, how do we interpret this?
🤔 Extraordinary proliferation of 2L options. Impossible to know today which is best
🤔 China-only studies needs global validation, as EGFR population different to rest of world
🤔 A biomarker driven option (SAFFRON) appealing, although only minority of patients MET OE/amp
🤔 Arrival of active ADCs very welcome, but biomarkers needed to better select patients
🤔 ADCs not necessarily less toxic than chemo: perhaps no increase in Gr3+, but a lot of Gr1-2 AEs
🤔 What is available 2L will impact on what we choose in 1L. In turn, what we choose 1L may impact on what we can use 2L (e.g. different MET alterations with Ami/Laz)

Conclusions: hugely complex. Only answerable with longer follow up & global studies.

#LCSM

— Tom Newsom-Davis (@tnewsomdavis) Oct 26, 2026

Context: his post lists PANKU-Lung01 experimental arm mPFS as 11.7 mo; LBA71 reports 11.1 mo.

SAFFRON

Savolitinib + osimertinib for MET-driven resistance after osimertinib. Savolitinib is investigational in the US. Grade ≥3 TRAEs 40% vs 52% (NEJM; DCO 6-Jul-2026).

Gilberto Lopes on SAFFRON:

Key message: Test for MET-mediated resistance. Adding MET inhibition while maintaining EGFR suppression improves survival in biomarker-selected disease.

Next: sequencing, CNS outcomes, and access.

Lu et al. ESMO LBA6 / NEJM 2026.

— gilberto lopes (@GlopesMd) Oct 25, 2026

Also posting on SAFFRON: Estela Rodriguez.

OptiTROP-Lung04

Sac-TMT vs chemotherapy. Final OS 25.9 vs 17.4 mo, HR 0.69 (LBA67, ESMO26; DCO 6-Aug-2026). China-only. Dato-DXd has FDA accelerated approval in EGFRm NSCLC after EGFR-directed therapy and platinum chemotherapy.

Estela Rodriguez on OptiTROP-Lung04:

🚨 #ESMO26 | OptiTROP-Lung04 (Phase III- China only trial)

Significant mOS 8.5 mo advantage for sac-TMT, a TROP2 ADC, after EGFR-TKI progression in EGFR-mutant NSCLC🫁 vs chemo!

📊 Median OS: 25.9 vs 17.4 months
🔥 HR 0.69 — 31% lower risk of death
⚠️ AEs- cytopenias, stomatitis, opthal, ILD

👉🏽Competes w Dato-DXd already approved in this EGFR+ population based on Tropion-Lung05, Lung01
👉🏽Global validation and treatment-sequencing questions remain.
@EGFRResisters
#LCSM #LungCancer #ESMO26

— Dr. Estela Rodriguez (@Latinamd) Oct 25, 2026

Also posting on OptiTROP-Lung04: Alfredo Addeo, MD, Stephen V Liu, MD and Gilberto Lopes.

PANKU-Lung01

Iza-bren (izalontamab brengitecan, BL-B01D1) vs platinum chemo (LBA71, ESMO26 / Lancet; DCO 15-Jul-2026). ORR 60.2% vs 34.5%. ILD 0.9%. TRAE discontinuation 1.9% in each arm. China-only. Investigational.

Stephen V Liu, MD, on PANKU-Lung01:

#ESMO26 Dr. Li Zhang presents PANKU-Lung01: phase III izalontamab brengitecan (iza-bren, HER3:EGFR ADC) vs platinum based chemo in EGFR+ NSCLC after 3G TKI. Iza bren improved PFS: 11.1 vs 5.7m, HR 0.40! OS immature but 1y rates 83% vs 73%. High reduction/interruption rates but low discontinuation rates. Most common toxicities were hematologic in nature. Very exciting data here: ADCs here to stay. #ESMOAmbassadors

— Stephen V Liu, MD (@StephenVLiu) Oct 26, 2026

Riyaz Shah on PANKU-Lung01:

PANKU-Lung01; iza-bren (bispecific EGFRxHer3 ADC; randomised P3 in common mEGFR and PD on 3rd gen; treated stable BM; n432: PFS HR 0.4: mOS NR in Ix arm but 19m in control; lots of dose adjustments ; ILD 0.9%. This looks like a new SOC I’d like to use in clinic. #ESMO26 https://t.co/GOS1jS7dev

— Dr Riyaz Shah (@DrRiyazShah) Oct 26, 2026

Also posting on PANKU-Lung01: Gilberto Lopes and Hidehito Horinouchi. Horinouchi also posted phase 2 data from 2575P (single-arm; investigational): iza-bren + osimertinib first line, ORR 100% in 40 patients at 2.5 mg/kg, ILD 1.3% overall (n=154).

HERON-Lung01

Ruzaltatug rezetecan (SHR-A2009) vs platinum chemo (LBA72, ESMO26 / Lancet; interim, DCO 15-Apr-2026). ORR 60% vs 34%. ILD 2.4%. China-only. Investigational.

Antonio Calles on HERON-Lung01:

HERON-Lung01: Ruzaltatug rezetecan (SHR-A2009), antiHER3 ADC, showed increased efficacy in terms of ORR and PFS, but OS not mature yet compared to pt-based chemotherapy. Significant toxicities. Not a SoC yet to me. #ESMO26 #LCSM https://t.co/r0feshFC5z

— Dr. Antonio Calles 🫁🚭 (@Tony_Calles) Oct 26, 2026

Tom John on HERON-Lung01:

C Xu: HERON Ph3 trial using HER3 ADC. Crossover permitted for this study. Also no TKI continuation. Another ADC meets it’s primary endpoint in EGFRm NSCLC. No biomarker data presented. Access will be key. #LCSM #ESMO26 https://t.co/VUCh0wGaG3

— Prof Tom John (@TommyJohn00) Oct 26, 2026

Also posting on HERON-Lung01: Stephen V Liu, MD, Riyaz Shah and Young Kwang Chae, MD.

PANKU-Lung01 and HERON-Lung01: discussion

Young Kwang Chae, MD, MPH, MBA, on Simon Ekman's discussion of LBA71 and LBA72:

Great discussion at #ESMO2026 by Dr. Simon Ekman (Karolinska University Hospital) addressing LBA71 (PANKU-Lung01) and LBA72 (HERON-Lung01): "Has the Achilles' heel been found?" 🧬🔍 

Key insights & questions raised on HER3-directed ADCs in post-EGFR TKI NSCLC: 
💡 Discussion Points:

• CNS Activity: Promising intracranial efficacy observed, though further evaluation of brain metastasis subgroup responses remains key.
• Predictive Biomarkers Needed: Beyond expression levels alone, addressing HER3 heterogeneity, membrane localization, linker stability, and payload mechanics.
• Algorithm Positioning: Determining exact optimal treatment sequencing and combination regimens post-3rd gen EGFR-TKI.
• Global Translatability outside China is the key. There are ongoing trials expanding to 1L combinations. 
#OncoTwitter #LungCancer #EGFR #NSCLC #Oncology #ESMO26 #MedicalResearch

— Young Kwang Chae, MD, MPH, MBA (@youngkwangchae) Oct 26, 2026

Also posting on both trials: Urs Weber MD and Alfredo Addeo, MD.

Also discussed

SARON: local consolidative therapy

SARON tested adding local consolidative therapy (LCT) in synchronous oligometastatic NSCLC. Per Newsom-Davis: PFS benefit, no OS benefit.

Tom Newsom-Davis on SARON:

Practice changing data from the SARON study at #ESMO26 from @fifimcdrmh @royalmarsdenNHS

👏 Herculean effort, run over 10 years
🤔 Does adding radiotherapy to SACT in the immunotherapy era improve survival in synchronous oligometastatic NSCLC?

What do we know already?
✅ LCT improves outcomes in pre-immuno era & with AGA+ NSCLC
❌ More recently, no survival benefit with niv/ipi regimens (LONESTAR)

What does SARON add?
✅ Well designed, randomised, multicentre prospective study
✅ Comprehensive baseline assessments with PET and MRI
✅ Appropriate definition of OMD (1-5 sites)
✅ PFS benefit, and reduces progression at treated sites
❌ No OS benefit, and no reduction progression at new sites of disease
✅ No additional toxicity

Thoughts:
🤔 Great academic 🇬🇧 study 👏
🤔 Addresses important & relevant question
🤔 Presumably parents have more metastases than we can detect, which then progress, losing OS benefit
🤔 Patients must be informed of lack of OS benefit if LCT being considered
🤔 Is LCT appropriate if OS not improved?
(❗️LCT in AGA+ NSCLC, and LCT in metachronous OMD not answered here)

#LCSM

— Tom Newsom-Davis (@tnewsomdavis) Oct 25, 2026

OptiTROP-Lung06: first-line PD-L1-negative

Sac-TMT + pembrolizumab vs chemo + pembrolizumab, first-line nonsquamous NSCLC, PD-L1-negative, no EGFR/ALK. PFS 15.0 vs 5.7 mo, HR 0.49 (LBA66, ESMO26 / NEJM; interim, DCO 9-Jun-2026). OS immature; median follow-up 9.7 mo. China-only. Sac-TMT is not FDA-approved.

Estela Rodriguez on OptiTROP-Lung06:

🇪🇸 #ESMO26 | Top Lung Abstracts 🫁

🚨 OPTITROP-Lung06: Phase III trial in PD-L1–negative, driver-negative nonsquamous NSCLC:

🔥 Median PFS: 15.0 vs 5.7 months
📉 HR 0.49 — 51% reduction in risk of progression/death
🎯 DOR: 13.6 vs 6.8 months
📊 12-mo OS: 77.6% vs 66.4% (immature data)

▶️ I wouldn’t call this a “chemo-free” regimen because the toxicity of an ADC is similar to chemo—> but this many be a potential option for this hard to treat PDL1 neg population.

▶️Could this change the 1L landscape? 👀maybe? but I would hope for a bigger survival advantage….data immature …

#LungCancer #LCSM #ADC

— Dr. Estela Rodriguez (@Latinamd) Oct 25, 2026

Also posting on OptiTROP-Lung06: Gilberto Lopes, Clive Peedell and Estela Rodriguez, who shared the NEJM paper.

FAQ

Is divarasib a new standard of care after KRASCENDO-1?

Divarasib is investigational. KRASCENDO-1: OS 17.7 vs 12.0 mo, HR 0.56; PFS 9.8 vs 5.7 mo, HR 0.58 (LBA5, ESMO26; DCO 19-May-2026). Tom Newsom-Davis on access: "Drug access will be the main issue, especially with Sotorasib withdrawal of funding in many countries."

Does PERSEE change first-line treatment for PD-L1 ≥50% NSCLC?

Chemo + pembrolizumab vs pembrolizumab alone: PFS 16.1 vs 6.9 mo, HR 0.56. Grade ≥3 TRAEs 54% vs 19%. Early progression at the first 6-week scan 5.8% vs 26.5% (exploratory) (2614O, ESMO26; DCO 7-Apr-2026). On patient selection, Tom Newsom-Davis wrote that he will now use chemo-pembro in PD-L1 above 80% for most patients, and that pembro alone still has a role in select PD-L1-high patients, especially above 90% with KRAS G12C.

Is tarlatamab + durvalumab now standard first-line maintenance in ES-SCLC?

Not yet FDA-approved. Tarlatamab is FDA-approved 2L+. DeLLphi-305: OS 21.1 vs 12.7 mo, HR 0.42 (LBA3, ESMO26). Christine Lovly called it practice changing and flagged equitable access. Julien Mazieres wrote that maintenance vs 2L tarlatamab will be discussed.

Are the EGFR ADCs from ESMO26 a new standard after EGFR TKI?

OptiTROP-Lung04, PANKU-Lung01 and HERON-Lung01 enrolled in China only. Tom Newsom-Davis: "China-only studies needs global validation, as EGFR population different to rest of world." Gilberto Lopes on PANKU-Lung01: "China-only trial; global validation and optimal sequencing remain important." Young Kwang Chae, summarizing Simon Ekman's discussion: "Global Translatability outside China is the key." None of these ADCs is FDA-approved. Sac-TMT is approved in China.

Go deeper

• KRASCENDO-1 trial page
• PERSEE trial page
• DeLLphi-305 trial page
• SAFFRON trial page
• OptiTROP-Lung04 trial page
• PANKU-Lung01 trial page
• HERON-Lung01 trial page
• OptiTROP-Lung06 trial page
• Top lung cancer trials at ESMO 2026
• ESMO 2026 lung cancer slide library
• ESMO 2026 day-by-day KOL Pulse toolkit
• All KOL Pulse trial pages