Head & Neck
Both trials hold the surgery + adjuvant CRT backbone constant; the new variable is the IO agent and its timing, not RT dose, volume, or fractionation.
KEYNOTE-689 vs NIVOPOSTOP
TL;DRTwo positive phase III IO trials in resectable LA-HNSCC: perioperative pembro (EFS+) vs postoperative nivo (3yr DFS ~63 vs 53%), both layered on surgery+adjuvant CRT.
Trials discussed
KEYNOTE-689NIVOPOSTOP
vs leading data
- PD-L1 CPS: higher CPS appears to derive greater benefit (KEYNOTE-689, per infographic)
7 details 2 trials watching
Methods
- 🔍 RT/CRT backbone is unchanged in both: the new variable is the IO agent and its timing, not RT dose, volume, or fractionation
- 🔍 KEYNOTE-689 schema: 2 cycles neoadjuvant pembro → surgery → adjuvant RT/CRT + pembro → maintenance pembro
- 🔍 NIVOPOSTOP (GORTEC 2018-01): high-risk resected → post-op cisplatin CRT ± nivo; high-risk = +margin, ENE, ≥4 nodes, extensive PNI
Results
- 📊 KEYNOTE-689 vs NIVOPOSTOP — design + headline (per infographic)
Feature KEYNOTE-689 NIVOPOSTOP IO agent Pembrolizumab Nivolumab Timing Perioperative (neoadj + adj + maint) Postoperative only Population Resectable Stage III-IVA High-risk resected (ENE, +margin, ≥4 nodes) Control arm Surgery → adj RT + cisplatin Post-op cisplatin CRT 1° endpoint Event-free survival Disease-free survival Headline EFS benefit (no number in source) 3-yr DFS ~63% vs 53% - 📊 KEYNOTE-689 positive for EFS; called first positive perioperative IO trial in resectable HNSCC in >2 decades. Effect size (HR/CI/median) not reported in source
Critique
- ⚠️ No RT technique parameters (dose, fractionation, target volume) reported in source; transferability to your plan can't be judged from this infographic
- ⚠️ Source is a secondary educational infographic, not primary trial data; HRs, CIs, and KEYNOTE-689 EFS magnitude not quantified
Open questions
- Perioperative pembrolizumab vs postoperative nivolumab: optimal IO timing untested head-to-head n=80 · primary completion 2029-02 · perioperative ivonescimab vs pembrolizumab in LA-HNSCCrecruiting Sintilimab Plus Chemotherapy as Neoadjuvant and Adjuvant Treatment for Locally Advanced Oral Squamous Cell Carcinoma Phase 3n=104 · primary completion 2030-12 · phase 3 perioperative sintilimab in resectable oral SCC
- PD-L1 CPS threshold for selecting IO benefit in resected HNSCC
- Whether adding IO changes adjuvant RT dose, volume, or fractionation
📚 Sources · 🐦 1 tweet
🧠 High-yield: KEYNOTE-689 vs NIVOPOSTOP
— Dr Rupam Manna MD (@DrRupamOncology) June 15, 2026
These two trials are redefining standards for resectable LA-HNSCC.
1/ KEYNOTE-689 (NEJM 2025)
Perioperative pembro → significant EFS benefit
First positive perioperative IO trial in >2 decades
2/ NIVOPOSTOP (ASCO 2025)
Post-op nivo +… pic.twitter.com/1mRQr9jmVX