In recent years, the standard of care in recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has shifted dramatically. Historically, the chemotherapy and cetuximab containing EXTREME regimen has been the preferred first-line treatment in this setting, though this regimen is associated with high rates of toxicity and can be difficult for patients to tolerate. More recently, immunotherapy with PD-1 and PD-L1 targeting immune checkpoint inhibitors has emerged as a safe and effective treatment alternative. In the randomized, phase III KEYNOTE-48 trial, the PD-1 inhibitor pembrolizumab was compared to cetuximab plus chemotherapy in 882 patients with untreated recurrent or metastatic SCCHN. Final results from this study were recently published in The Lancet.
Patients received either pembrolizumab monotherapy, pembrolizumab in combination with chemotherapy, or cetuximab plus chemotherapy. In patients with a PD-L1 combined positive score (CPS) ≥ 20, pembrolizumab monotherapy significantly improved overall survival (OS) compared to cetuximab plus chemotherapy (14.9 months vs 10.7 months; HR 0.61, P = .0007). Pembrolizumab monotherapy also improved median OS in the cohort with PD-L1 CPS ≥ 1 (12.3 months vs 10.3 months; HR 0.78, P = .0086). There was also a significant benefit for OS in patients receiving pembrolizumab plus chemotherapy compared to cetuximab plus chemotherapy, regardless of PD-L1 expression. In the total patient population, pembrolizumab plus chemotherapy resulted in a median OS of 13.0 months, compared to 10.7 months with cetuximab plus chemotherapy (HR 0.77, P = .0034). There was no progression-free survival (PFS) benefit for pembrolizumab either alone or in combination with chemotherapy.
Adverse events (AEs) were manageable and consistent with the known safety profile of pembrolizumab. Importantly, AEs occurred less frequently in patients receiving pembrolizumab monotherapy compared to those receiving cetuximab plus chemotherapy. AEs of grade 3 or higher occurred in 55% of patients receiving pembrolizumab monotherapy, 85% of patients receiving pembrolizumab plus chemotherapy, and 83% of patients receiving cetuximab plus chemotherapy.
The investigators concluded that these results support pembrolizumab as monotherapy or in combination with chemotherapy as a new standard of care in patients with recurrent/metastatic SCCHN. In a commentary accompanying this report, experts agreed that pembrolizumab has earned a place as a new standard of care for SCCHN, but indicated many questions still remain. Importantly, guidance on which patient should receive pembrolizumab monotherapy versus combination with chemotherapy and strategies to improve the response rate and PFS will be needed.
Read more about this study on Medscape Medical News.
Lancet. 2019 Oct 31. [Epub ahead of print.]