Ali Chamseddine: Top 10 Practice-Changing Insights from ESMO 2026

Ali Chamseddine, Consultant Medical Oncologist and Clinical Hematologist at Al Zahra Pvt. Hospital Dubai, shared on X:

“The 10 trials that matter most

Ranked on hard endpoint, effect on practice, size of the population and weight in Madrid – author’s judgement

1. DeLLphi-305

ES-SCLC · LBA3 · NEJM

• Setting and comparison: After 4 cycles platinum-etoposide + durvalumab: tarlatamab + durvalumab vs durvalumab (n = 563)
• Key result: OS 21.1 vs 12.7 mo, HR 0.42; PFS HR 0.34
• Why it matters: Largest OS effect of the congress; a T-cell engager moves into first-line maintenance
• Caveat: Interim; CRS 49.6% (grade ≥3 0.4%)
• Verdict: Change when accessible

Find out more:

DeLLphi-305: Tarlatamab–Durvalumab Redefines First-Line Maintenance in Extensive-Stage SCLC

2. VOLGA

MIBC · LBA2 · NEJM

• Setting and comparison: Cisplatin-ineligible: durvalumab + EV × 3 → cystectomy → durvalumab vs cystectomy (3 arms, n = 695)
• Key result: EFS HR 0.51; OS HR 0.58; 24-mo OS 78.4% vs 69.4%
• Why it matters: Third positive perioperative EV + IO trial, effective without adjuvant EV
• Caveat: Adding tremelimumab: OS HR 0.77, NS
• Verdict: Change when accessible

Find out more:

VOLGA at ESMO 2026: Perioperative Durvalumab With or Without Tremelimumab Plus Enfortumab Vedotin in MIBC

3. INTerpath-001

Melanoma · LBA1

• Setting and comparison: Resected stage IIB–IV: intismeran (individualised mRNA) + pembrolizumab vs pembrolizumab (n = 1,137)
• Key result: RFS HR 0.58; 24-mo RFS 82.2% vs 70.0%
• Why it matters: First phase 3 win for a personalised cancer vaccine
• Caveat: OS immature (HR 0.77); 64 days to first dose
• Verdict: Promising, wait

Find out more:

INTerpath-001 Trial: Personalized mRNA Cancer Vaccine in High-Risk Melanoma

4. TroFuse-005

Endometrial · LBA11 · Lancet

• Setting and comparison: After platinum and anti-PD-(L)1: sac-TMT vs doxorubicin or paclitaxel (n = 776)
• Key result: OS 19.0 vs 12.1 mo, HR 0.68; PFS HR 0.59
• Why it matters: First OS-positive ADC in this setting, mostly pMMR
• Caveat: Stomatitis 57% (any grade); steroid mouthwash
• Verdict: Change when accessible

Find out more:

TroFuse-005 at ESMO 2026: Sacituzumab Tirumotecan Significantly Improves Overall Survival in Advanced Endometrial Cancer

5. Krascendo-1

NSCLC · LBA5 · NEJM

• Setting and comparison: Pretreated KRAS G12C: divarasib vs sotorasib or adagrasib (n = 338)
• Key result: OS 17.7 vs 12.0 mo, HR 0.56; PFS HR 0.58
• Why it matters: First head-to-head OS win for a next-generation KRAS inhibitor, with less toxicity
• Caveat: Open-label; few adagrasib controls (n = 15)
• Verdict: Change when accessible

6. HARMONI-GI1

Biliary · LBA8

• Setting and comparison: 1L: ivonescimab vs durvalumab, each + gem-cis, double-blind (n = 682)
• Key result: OS 14.9 vs 12.1 mo, HR 0.75; PFS HR 0.61
• Why it matters: A PD-1×VEGF bispecific beats an approved IO regimen head to head
• Caveat: China only; grade 3–4 TEAEs 82.0% vs 72.3%
• Verdict: Promising, wait

Find out more:

HARMONi-GI1 at ESMO 2026: Ivonescimab Plus Chemotherapy in Advanced Biliary Tract Cancer

7. SAFFRON + SANOVO

EGFR NSCLC · LBA6 · LBA69

• Setting and comparison: MET overexpressed: osimertinib + savolitinib vs chemo after osimertinib (n = 338) and vs osimertinib in 1L (n = 326)
• Key result: SAFFRON OS HR 0.68; SANOVO PFS HR 0.56, OS HR 0.48
• Why it matters: MET testing becomes routine in EGFR-mutant disease
• Caveat: SANOVO OS at 40.5% maturity
• Verdict: Practice-changing

Find out more:

SAFFRON Phase III: Osimertinib Plus Savolitinib Significantly Improves Progression-Free and Overall Survival in MET-Driven EGFR-Mutated NSCLC

8. DASL-HiCaP

Prostate · LBA4

• Setting and comparison: Very-high-risk localised or salvage: darolutamide vs placebo + ADT + RT (n = 1,106)
• Key result: MFS HR 0.42; 4-y MFS 95% vs 88%
• Why it matters: First ARPI win with RT after ENZARAD was negative
• Caveat: Interim; OS HR 0.88; new very-high-risk definition
• Verdict: Promising, wait

Find out more:

DASL-HiCaP Trial Shows Darolutamide Improves Metastasis-Free Survival in Very High-Risk Prostate Cancer

9. KEYNOTE-C93

Endometrial · LBA12 · Lancet

• Setting and comparison: 1L dMMR: pembrolizumab alone vs carboplatin-paclitaxel (n = 299)
• Key result: PFS 38.2 vs 8.4 mo, HR 0.57; grade ≥3 TRAEs 18.1% vs 50.7%
• Why it matters: Proof that chemotherapy-free first line works in dMMR
• Caveat: Outdated comparator; curves cross at ~6 mo; OS HR 0.77
• Verdict: Promising, wait

Find out more:

KEYNOTE-C93 Trial: Pembrolizumab Versus Chemotherapy in dMMR Endometrial Cancer

10. MOIO

Pan-tumour · LBA10

• Setting and comparison: ICI responders at 6 months: same ICI every 12 weeks vs standard (n = 340)
• Key result: PFS HR 1.35 (non-inferiority not shown); OS HR 2.04
• Why it matters: The key negative: spacing immunotherapy is not safe
• Caveat: First interim; 14 tumour types
• Verdict: Stop doing

Find out more:

MOIO Trial: Can Immunotherapy Be Given Less Frequently?

Close behind

NATALEE 6-year OS (HR 0.809), HEALER (anbenitamab vs THP, PFS HR 0.46, NEJM), PEACE-1 long-term (abiraterone with ADT + docetaxel: 8-y OS 40.3% vs 27.1%), CLARITY-Gastric01 (CLDN18.2 ADC, 3L+ OS HR 0.47), ARTEMIS-011 (osteosarcoma, PFS HR 0.33), OptiTROP-Lung06 (sac-TMT + pembrolizumab, PFS HR 0.49)

Three themes behind the list:

• ADCs now beat chemotherapy across five tumour types.
• Bispecifics are starting to beat established drugs head to head (tarlatamab, ivonescimab).
• De-escalation has to be proven, not assumed (KEYNOTE-C93 cautiously yes, MOIO no).”

You can also read:

ESMO 2026 Presidential Symposia: From Trial Results to Clinical Implications