Pembrolizumab in the first-line treatment of advanced head and neck cancer

ABSTRACT

Introduction

Recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis and has limited therapeutic options. PD-1/PD-L1 axis blockade was initially shown to improve outcomes in platinum-refractory HNSCC. More recently, pembrolizumab monotherapy or pembrolizumab combined with chemotherapy resulted in better overall survival than platinum, 5-fluorouracil, and cetuximab (EXTREME regimen) as first-line therapy for R/M HNSCC, establishing a new standard-of-care therapy for this disease.

Areas covered

We review pembrolizumab in the first-line treatment of R/M HNSCC and summarize the impact of PD-L1 expression, tumor and symptom burden, and patient’s performance status on treatment decisions. Future perspectives are summarized.

Expert opinion

The standard-of-care first-line therapy for R/M HNSCC is pembrolizumab monotherapy for patients with a PD-L1 combined positive score (CPS)≥1 or pembrolizumab combined with platinum and 5-fluorouracil for patients with any PD-L1 status. Addition of chemotherapy to pembrolizumab increases the response rate but also toxicity and is preferred for patients with good performance status and significant tumor and symptom burden. For patients with a PD-L1 CPS <1, the EXTREME regimen should be considered. New strategies combining pembrolizumab with targeted therapies and immune checkpoints inhibitors are being explored to synergize or overcome resistance to anti-PD-1.

KEYWORDS:

• Head and neck squamous cell carcinoma
• immune checkpoint inhibitor
• immunotherapy
• palliative care
• PD-1 inhibitor
• pembrolizumab

Article highlights

• Pembrolizumab is associated with improved survival, longer response duration, and a better toxicity profile than cetuximab plus chemotherapy (EXTREME regimen) in the first-line treatment of R/M HNSCC patients with PD-L1 CPS ≥1

• Addition of chemotherapy to pembrolizumab doubles the response rate (from 17% for pembrolizumab monotherapy to 36% for pembrolizumab plus chemotherapy) and is associated with better survival than chemotherapy plus cetuximab in the first-line treatment of patients with R/M HNSCC irrespective of PD-L1 status

• Although pembrolizumab plus chemotherapy has shown an overall survival benefit in biomarker-unselected R/M HNSCC patients, the benefit of pembrolizumab is mostly driven from tumors with PD-L1 CPS ≥1, therefore, the EXTREME regimen remains an acceptable option for patients with CPS<0

• In patients with R/M HNSCC with PD-L1 CPS ≥1, performance status and disease and symptom burden should guide the choice of pembrolizumab monotherapy or pembrolizumab combined with chemotherapy

• Ongoing clinical trials are investigating pembrolizumab in combination with other immune checkpoint inhibitors or targeted therapies to synergize with or overcome resistance to anti-PD-1

Acknowledgments

The authors would like to thank Stephanie Deming, scientific editor, Research Medical Library, for editing this article.

Declaration of interest

R Ferrarotto reports personal fees from Regeneron-Sanofi, Ayala Pharmaceuticals, Prelude Pharmaceuticals, Bicara Therapeutics, Klus Pharma, Medscape, and Carevive and institutional fees from AstraZeneca, Merck, Genentech, Pfizer, EMD-Serono, Ayala Pharmaceuticals, Prelude Pharmaceuticals, and Rakuten Medical not related to the topic of the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

LG Sousa contributed to data collection, interpretation, and writing. R Ferrarotto contributes to data interpretation, reviewing, and writing.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The authors have no funding to report.