Pembrolizumab Becomes First Approved Perioperative Immunotherapy for Resectable HNSCC in Canada

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Merck has announced that Health Canada has approved pembrolizumab (KEYTRUDA) for the perioperative treatment of adults with resectable, locally advanced head and neck squamous cell carcinoma whose tumours express PD-L1 (CPS ≥1).¹ This marks the first Health Canada-approved perioperative immunotherapy regimen for this patient population.

The approval is based on findings from the Phase III KEYNOTE-689 trial (NCT03765918), a randomized, multicenter, open-label study involving 714 patients with Stage III–IVA head and neck squamous cell carcinoma. The trial evaluated pembrolizumab given neoadjuvantly, followed by adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin, and then as monotherapy maintenance.

Treatment Protocol

Patients in the pembrolizumab arm received:

• Neoadjuvant pembrolizumab (200 mg x 2 doses every 3 weeks) before surgery.
• Post-operative pembrolizumab (3 cycles) in combination with:
• RT + cisplatin for patients with high-risk pathological features (positive margins or extranodal extension), or
• RT alone for those without high-risk features.
• This was followed by pembrolizumab monotherapy every 3 weeks for up to 12 additional cycles, for a total of 17 cycles.

The comparator group received standard post-surgical treatment (RT ± cisplatin) without neoadjuvant pembrolizumab or maintenance immunotherapy.

Clinical Impact

The primary endpoint was event-free survival by Blinded Independent Central Review (BICR), with an additional measure of overall survival. KEYNOTE-689 demonstrated that the addition of pembrolizumab significantly improved event-free survival in patients with PD-L1-positive tumors. Specifically, patients receiving perioperative pembrolizumab had a 30% reduction in the risk of events (HR = 0.70; 95% CI: 0.55–0.89; p = 0.0014) compared to those receiving standard therapy without neoadjuvant immunotherapy. The median event-free survival was 59.7 months in the pembrolizumab arm, compared to 29.6 months in the control arm.

"We know that head and neck squamous cell carcinomas present significant treatment challenges because of their complexity," André Galarneau, PhD, Executive Director & Vice President of the Oncology Business Unit at Merck Canada, said in a press release. "The introduction of a perioperative anti-PD-1 treatment option for eligible patients in Canada represents an important development with the potential to make a meaningful difference for patients and their families impacted by this disease."¹

Safety Profile

The most common treatment-related adverse events in the pembrolizumab group were radiation skin injury and stomatitis, which occured in at least 20% of patients. Grade 3 to 5 events included stomatitis (11.6%), decreased lymphocyte count (5.5%), and decreased neutrophil count (5.3%). These were reported in at least 5% of patients. Overall, the safety profile was consistent with previous studies of pembrolizumab.

Conclusion

In Canada, approximately 8,100 new cases of head and neck squamous cell carcinoma were diagnosed in 2024, with over 2,100 deaths reported, according to Merck’s statement. Pembrolizumab, which was first approved in Canada in 2015, now holds indications across a wide spectrum of cancers. Its mechanism of action, blocking PD-1 and PD-L1 interactions, enhances T-cell activity, aiding immune recognition and elimination of tumor cells. This latest approval represents a significant advancement in the treatment landscape for head and neck squamous cell carcinoma, offering new hope for long-term disease control in patients with resectable, locally advanced, PD-L1-positive tumors.

References

1. Health Canada Approves KEYTRUDA® for Patients with Resectable Locally Advanced Head & Neck Squamous Cell Carcinoma Tumours that are PD-L1 (CPS) Positive as Neoadjuvant Treatment, Continued as Adjuvant Treatment Combined With Radiotherapy With or Without Cisplatin Then as Monotherapy. News release. BioSpace. Published August 13, 2025. Accessed August 13, 2025. https://www.biospace.com/press-releases/health-canada-approves-keytruda-for-patients-with-resectable-locally-advanced-head-neck-squamous-cell-carcinoma-tumours-that-are-pd-l1-cps-positive-as-neoadjuvant-treatment-continued-as-adjuvant-treatment-combined-with-radiotherapy-with-or-without-cisplatin-then-as-monotherapy