Fabio Ynoe de Moraes, Radiation Oncologist and Associate Professor at Queen’s University, shared a post on LinkedIn:
“Recap ESMO 2025 – Lung/ Brain/ SBRT focus
If you blinked during ESMO 2025, you might’ve missed the studies that could reshape lung cancer care.
From stage III setbacks to surprising conversions in unresectable disease—and the biomarkers that still elude us—the Berlin congress delivered high-stakes insights for everyone in thoracic oncology.
Here’s my quick take on the trials you don’t want to overlook…
1. SKYSCRAPER-03 (LBA69) – Atezolizumab + Tiragolumab vs Durvalumab in Stage III NSCLC
Design: Phase III, open-label, randomized (N=829)
Population: Unresectable stage III NSCLC without progression after concurrent chemoradiotherapy (CRT)
Key Result: No PFS or OS benefit with dual PD-L1 + TIGIT blockade vs durvalumab alone.mPFS (all-comers): 14.2 vs 13.8 months (HR 1.00)mOS (all-comers): 45.6 vs 45.8 months (HR 0.98)
Implication: Reinforces durvalumab post-CRT as standard of care; TIGIT inhibition not practice-changing in this setting.
2. LungMate-013 (Abstract 1818MO) – Induction Serplulimab + Chemo → Surgery vs Radiotherapy
Design: Phase II, randomized, open-label (N=100 induction; 50 randomized)
Population: Initially unresectable stage IIIB–IIIC NSCLC
Key Finding: After induction immunochemotherapy, conversion to resectability occurred in ~50%. EFS favored surgery over radiotherapy:ITT: HR 0.38 (95% CI 0.14–1.01)Per-protocol: HR 0.21 (95% CI 0.06–0.66)
Relevance to you: Directly intersects with SBRT and resectability paradigms—raises questions about local therapy selection post-induction in borderline resectable cases.
3. PACIFIC-9 (LBA70) – Durvalumab + Oleclumab (anti-CD73) in Stage III NSCLC
Background: CD73 is an immunosuppressive enzyme in the adenosine pathway.
Result: No significant improvement in PFS vs durvalumab alone.
Takeaway: Another failed combo strategy in stage III; highlights difficulty of improving on PACIFIC backbone.
4. NeoCOAST-2 (LBA71) – Neoadjuvant Dual Immunotherapy in Resectable NSCLC
Regimens tested: Durvalumab ± oleclumab, monalizumab (anti-NKG2A), or danvatirsen (STAT3 inhibitor)
Key Result: Pathological complete response (pCR) rates highest with durvalumab + monalizumab (~35% vs ~19% with durvalumab alone).
Implication: May influence neoadjuvant approaches, though long-term survival data pending.
5. MARIPOSA-2 Subgroup Analysis (Late-Breaking) – Amivantamab + Chemo in EGFR-mutant NSCLC Post-Osimertinib
Finding: Confirmed PFS benefit in patients with EGFR exon 19 del/L858R after osimertinib failure.
Median PFS: 7.4 vs 4.2 months (chemo alone)
Relevance: Important for sequencing in EGFR+ NSCLC, especially with CNS progression (given amivantamab’s CNS activity).
6. Biomarker Studies
- TACTI-002 Biomarker Correlatives: Highlighted that TIGIT expression alone is insufficient to predict response to tiragolumab—supports Faivre-Finn’s call for better biomarkers in stage III disease.
- ctDNA Clearance Post-Induction: In LungMate-013 and other trials, ctDNA negativity after inductionstrongly correlated with improved EFS—potential tool for guiding local therapy decisions (e.g., surgery vs SBRT vs conventional RT).
Clinical Implications (SBRT/Brain Mets Focus):
- Stage III: Durvalumab remains standard; no role yet for TIGIT inhibitors or CD73 blockade.
- Borderline Resectable Disease: Induction immunochemotherapy may convert some to operable status—but SBRT could be an alternative for those unfit for surgery. Trials defining SBRT’s role post-induction are needed.
- CNS Considerations: While not detailed in these abstracts, systemic regimens with CNS penetration(e.g., amivantamab, next-gen TKIs) are increasingly relevant for brain mets—stay tuned for CNS-specific subgroup analyses.
Upcoming Trials to Watch:
- PACIFIC-4: Testing durvalumab in unresectable stage II NSCLC (potentially practice-changing for your SBRT cohort).
- KEYNOTE-999: Pembrolizumab + chemoradiation in stage III (results expected 2026).”
More posts featuring Fabio Ynoe de Moraes.