
Amol Akhade: Exciting update from AACR25
Amol Akhade, Consultant Medical Oncologist and Hemato-oncologist at Suyog Cancer Clinics, posted on LinkedIn:
“Exciting update from AACR25!
KEYNOTE-689 trial delivers promising results for patients with resectable locally advanced HNSCC (head and neck squamous cell carcinoma) undergoing perioperative immunotherapy!
Here’s the snapshot:
- Study Design
- Resectable Stage III/IVA HNSCC
- 2 cycles of neoadjuvant pembrolizumab, followed by surgery
- Then adjuvant pembrolizumab + radiotherapy (± cisplatin)
- Stratified by PD-L1 TPS (<50% vs ≥50%)
Key Results
- Primary Endpoint: Event-Free Survival (EFS)
- HR 0.73 (95% CI 0.58–0.92), P = 0.0041 Median EFS: 51.8 months (pembro + SOC) 30.4 months (SOC alone)
- In CPS ≥10 subgroup
- HR 0.66 (95% CI 0.49–0.88), P = 0.0022 2-year EFS rates: 74% (pembro) vs 60% (SOC)
Benefit across most subgroups: Oropharynx, oral cavity, larynx tumors showed strong improvements Tumor stage III patients derived the most benefit (HR 0.42!).
Points to Note
- Hypopharynx subset showed uncertain benefit (small numbers, caution needed)
- Female patients showed no clear benefit (limited n, requires validation)
- 12 cycles of adjuvant pembrolizumab is quite long – future strategies may explore de-escalation
- OS data pending — long-term outcomes eagerly awaited!
Why is KEYNOTE-689 Important?
First large randomized trial showing perioperative immunotherapy improves outcomes in resectable HNSCC. Early KM curve separation and sustained benefit suggest durable responses. May define a new treatment paradigm beyond traditional surgery and radiotherapy alone.
My Take:
“KEYNOTE-689 positions perioperative pembrolizumab as a potential new standard in resectable LA-HNSCC, but thoughtful patient selection and long-term OS follow-up will be key.””
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