Can Perioperative Pembrolizumab Improve Outcomes in Locally Advanced Head and Neck Cancer?

Immune checkpoint inhibitors (ICIs) have established roles in recurrent and metastatic squamous cell carcinoma of the head and neck (HNSCC), whereas ICIs combined with definitive chemoradiation failed to improve outcomes in the curative-intent, locally advanced setting. To explore a role for perioperative administration of ICIs, investigators randomized more than 700 patients newly diagnosed with resectable locally advanced HNSCC to receive standard-of-care treatment (surgery plus adjuvant radiotherapy with or without cisplatin) either alone or with perioperative pembrolizumab (2 cycles neoadjuvant followed by 15 cycles adjuvant starting with radiation). Results of the industry-funded, multicenter, phase 3 KEYNOTE-689 trial were as follows:

• Patients who received pembrolizumab maintained longer event-free survival (EFS) at 3 years than those who did not (58% vs. 46%; hazard ratio, 0.73). Overall survival trended favorably (68% vs. 61% at 3 years; HR, 0.76).
• All patients benefited regardless of PD-L1 expression levels, but those whose percentage of tumor cells and immune cells containing PD-L1 (CPS) was ≥10 appeared to benefit the most (3-year EFS, 60% vs. 46% HR, 0.66). More patients in the pembrolizumab group than the control group had a major pathological response (9% vs. none).
• Adverse events were manageable and consistent with the known pembrolizumab safety profile, although immune-related adverse events occurred more frequently with pembrolizumab.