Introduction: Programmed death 1 (PD-1) blockade has changed the therapeutic landscape of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) with convincing overall response rates and overall survival benefits when compared to chemotherapy alone. The toxicity profile of pembrolizumab appears to be similar to that of other PD-1 or PD-L1 inhibitors, with frequent diarrhea, hypothyroidism or cutaneous rash cases, and rare cases of grade 3 to 5 pneumonitis.
Areas covered: In this article, the pharmacokinetics and mechanism of action of pembrolizumab will be covered, as well as the rationale behind tumor PD-L1 scoring. Safety and efficacy data surrounding pembrolizumab use will be presented. A tentative comparative analysis with other PD-1 (nivolumab) and PD-L1 (durvalumab) inhibitors will also be performed.
Expert opinion: Superior OS for pembrolizumab as first-line monotherapy was demonstrated in the CPS ≥ 20 and CPS ≥ 1 populations, with favorable toxicity profile when compared to the EXTREME regimen. Patient selection through adequate PD-L1 scoring is thus essential in order to limit upfront exposure to combination chemotherapy. Further trials are currently investigating the safety of PD-L1 inhibitors, alone or in combination with anti-CTLA-4 therapies.
Keywords: Head and neck cancer; PD-1 inhibitor; checkpoint inhibitor; immunotherapy; pembrolizumab.