🚨⭐🟠 #ESMO26 | Abstract 4736O | ENERGIZE (CA017-078)
Phase III trial of neoadjuvant chemotherapy ± nivolumab followed by adjuvant nivolumab in muscle-invasive bladder cancer (MIBC)
🎤 Presented by @AndreaNecchi 🇮🇹
@OncoAlert @urologysummit

🔬 Can perioperative nivolumab improve outcomes in patients with cisplatin-eligible MIBC?

📊 STUDY DESIGN
Phase III randomized trial | N=653
🔹 Nivolumab + gemcitabine/cisplatin → radical cystectomy → adjuvant nivolumab (n=325)
🔹 Gemcitabine/cisplatin → radical cystectomy → observation (n=328)

📊 KEY RESULTS

❌ Event-free survival (co-primary endpoint)
• Median EFS: NR vs 67.6 months
• HR 0.94 (95% CI 0.72–1.24)
• p=0.6697
➡️ No statistically significant improvement.
📈 Pathological complete response (co-primary endpoint)
• pCR: 39.1% vs 29.6%
• Absolute difference: +9.5 percentage points
❌ Did not meet the prespecified multiplicity-adjusted significance threshold.
🔬 Combined pathological response (≤ypT1N0)
• 51.7% vs 41.8%

🧬 ctDNA EXPLORATORY ANALYSIS
✅ Neoadjuvant ctDNA clearance:
• 81.3% vs 71.7%

📌 Pretreatment ctDNA positivity was associated with shorter EFS and OS.

However, no clear differential treatment benefit was observed according to baseline ctDNA status.
📊 Overall survival
• OS data remain immature.
• No established survival advantage.
⚠️ Safety was consistent with the known profiles of the individual agents.
🔬 CONCLUSION
Adding perioperative nivolumab to neoadjuvant gemcitabine/cisplatin did not significantly improve the co-primary endpoints of pCR or EFS in patients with MIBC.

⭐ MY POINT OF VIEW | CLINICAL PEARL
Improving pathological response does not necessarily translate into better long-term outcomes.
ENERGIZE reinforces an essential principle in perioperative oncology: pCR signals must be interpreted alongside EFS, OS, toxicity and statistical robustness.
🧬 ctDNA is emerging as a powerful prognostic biomarker, but its ability to guide treatment intensification or de-escalation still requires prospective validation.

💡 The future of perioperative MIBC treatment is not simply adding more immunotherapy. It is identifying who truly benefits—and who can safely avoid unnecessary treatment.
🌍 GU Oncology Community
@gbanna74 @ravikanesvaran
@tompowles1 @PGrivasMDPhD @apolo_andrea @sonpavde @montypal @TiansterZhang @DrYukselUrun @drenriquegrande @cdanicas

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#BladderCancer #MIBC #GUOncology #ClinicalTrials #OncoAlert