At the ESMO Congress 2026, Thiago B. Oliveira (São Paulo, Brazil) presented results from the phase II SMART-KEY (LACOG 0720) trial (NCT04943445), evaluating a pembrolizumab-based, cisplatin-free organ preservation strategy in patients with locally advanced laryngeal squamous cell carcinoma.
The investigational regimen achieved a 2-year laryngectomy-free survival (LFS) rate of 65.1%, with an 86% larynx preservation rate and 74.4% overall survival at two years. These outcomes were numerically comparable to historical results from established cisplatin-based organ preservation strategies.
Methods
SMART-KEY was a multicenter, single-arm phase II study evaluating whether pembrolizumab could support laryngeal preservation without concurrent cisplatin-based chemoradiotherapy.
The trial enrolled patients with newly diagnosed stage III–IVB glottic or supraglottic squamous cell carcinoma.
A total of 43 patients from nine centers received a three-phase treatment strategy:
- Induction therapy: Carboplatin (AUC 6), paclitaxel (175 mg/m²), and pembrolizumab (200 mg) for three 21-day cycles.
- Concurrent treatment: Intensity-modulated radiation therapy (IMRT) with pembrolizumab, without concurrent chemotherapy.
- Consolidation therapy: Fourteen additional 21-day cycles of pembrolizumab.
The primary endpoint was 2-year laryngectomy-free survival. Secondary outcomes included larynx preservation, laryngeal dysfunction-free survival, overall survival, recurrence, and treatment-related toxicity.
Key Takeaways
Between February 2022 and August 2023, 43 patients were enrolled. The median age was 61.1 years, 86% were male, and 83.7% were former or current smokers.
- Laryngectomy-free survival: The 2-year LFS rate was 65.1% (80% CI, 54.9–73.5%), compared with 64.9% reported in the historical RTOG 9111 trial.
- Larynx preservation: The 2-year larynx preservation rate was 86%, compared with 88% in RTOG 9111 and 75.8% in GORTEC 2000-01.
- Laryngeal dysfunction-free survival: The 2-year rate was 83.7%, compared with 70.3% in GORTEC 2000-01.
- Overall survival: The 2-year OS rate was 74.4%, compared with 74% in RTOG 9111 and 73% in GORTEC 2000-01.
- Locoregional recurrence: The 2-year cumulative incidence was 18.8%.
- Distant recurrence: The 2-year cumulative incidence was 7.4%.
- Treatment-related toxicity: Grade ≥3 treatment-related adverse events occurred in 41.9% of patients, including one grade 5 event.
- Immune-related toxicity: Grade ≥3 immune-mediated treatment-related adverse events occurred in 16.3% of patients.
At two years, 65.1% of patients were alive with their larynx preserved, while 9.3% were alive following laryngectomy.
Conclusion
The phase II SMART-KEY trial demonstrated that a pembrolizumab-based, cisplatin-free strategy achieved encouraging oncologic and functional outcomes in patients with locally advanced laryngeal cancer.
The 65.1% 2-year laryngectomy-free survival rate, together with an 86% larynx preservation rate, was numerically comparable to outcomes reported in historical cisplatin-based trials. The regimen also demonstrated a relatively low incidence of distant recurrence.
However, the single-arm design and small sample size prevent definitive conclusions about comparative efficacy or safety. Cross-trial comparisons should be interpreted cautiously, and the occurrence of severe treatment-related adverse events, including one treatment-related death, remains clinically important.
Further follow-up is needed to determine whether this cisplatin-free approach can reduce the long-term morbidity and mortality associated with conventional chemoradiotherapy while maintaining effective disease control.
Source: ESMO Congress 2026, Abstract 1537RO; SMART-KEY/LACOG 0720 (NCT04943445).
