Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012

Abstract

Some patients received 2 years of treatment and the responses were ongoing for more than 30 months; the durable anti-tumour activity and tolerable safety profile, observed with long-term follow-up, support the use of pembrolizumab as a treatment for recurrent/metastatic HNSCC.

Impact of PD‐L1 expression and human papillomavirus status in anti‐PD1/PDL1 immunotherapy for head and neck squamous cell carcinoma—Systematic review and meta‐analysis

“…Indications for pembrolizumab recently changed when the FDA granted approval as first‐line treatment for patients with R/M HNSCC regardless of prior treatment; individuals whose tumors express PD‐L1 can receive pembrolizumab monotherapy, but individuals without expressivity receive pembrolizumab in combination with other standard agents . This divergence in treatment regimen was based upon the finding that individuals whose tumors expressed PD‐L1, defined by a Combined Positive Score (CPS) ≥1 (a measure of the extent of expressivity in tumor and immune cells), had enriched responses and a favorable overall survival compared with those whose tumors were non‐expressive . However, whether this observed benefit is maintained across studies using various PD‐1/L1 targeting antibodies, each with particular PD‐L1 detecting techniques, is not well understood and was addressed herein.…”

“…Clinical trials of R/M HNSCC patients receiving monotherapy PD‐1/L1 blockade have demonstrated variable outcomes among patients stratified by PD‐L1 expression and HPV status . However, these trials have utilized a variety of methodologies for determining PD‐L1 and HPV expression, and further reported various cutoff points for determining PD‐L1 “positivity.” These inconsistencies are largely owing to the absence of a standardized method for quantifying PD‐L1 expression and determining an appropriate cutoff level to dichotomize patients.…”

Novel immune‐modulating drugs for advanced head and neck cancer

“…In R/M HNSCC patients who failed first‐line treatment, current evidence suggests that nivolumab results in prolonged OS and a more durable response compared to chemotherapy. Results of pembrolizumab trials suggest similar benefits . ICI therapy is also associated with a reduction in severe AEs, being more tolerable than standard chemotherapy.…”

“…Given the initial success of immunotherapy in various cancer types, much effort has been made to develop the immunotherapy concept in R/M HNSCC. Two PD‐1 immune checkpoint inhibitors (pembrolizumab and nivolumab) have been approved by the U.S. FDA for use in R/M HNSCC patients who fail on prior platinum‐based chemotherapy . Immunotherapy has been shown to provide a durable response with less frequent grade III/IV adverse events (AEs) compared with chemotherapy.…”

Serious immune‐related adverse events in patients with head and neck cancer after checkpoint blockade: Systematic review

“…Considering these 3 reports together, pembrolizumab caused trAEs of any grade in 226 out of 363 HNC patients (62.2%) and serious (grade ≥ 3) trAEs in 48 (13.2%) of these patients. Mehral et al reported the use of pembrolizumab in 192 patients in a multicenter, nonrandomized trial including two head and neck squamous cell carcinoma (HNSCC) cohorts (initial and expansion); pembrolizumab (10 mg/kg every 2 weeks, initial cohort n = 60 or pembrolizumab (200 mg every 3 weeks, expansion cohort n = 132). Of these, 13% reported grade ≥ 3 trAEs, vs 64% of the patients with trAEs of any grade.…”