Abstract
BackgroundSecond-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up.MethodsMulti-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks (initial cohort; N = 60) or 200 mg every 3 weeks (expansion cohort; N = 132). Co-primary endpoints were safety and overall response rate (ORR; RECIST v1.1; central imaging vendor review).ResultsMedian follow-up was 9 months (range, 0.2–32). Treatment-related adverse events (AEs) of any grade and grade 3/4 occurred in 123 (64%) and 24 (13%) patients, respectively. No deaths were attributed to treatment-related AEs. ORR was 18% (34/192; 95% CI, 13–24%). Median response duration was not reached (range, 2+ to 30+ months); 85% of responses lasted ≥6 months. Overall survival at 12 months was 38%.ConclusionsSome 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.
Highlights
Treatment options were limited for patients with advanced head and neck squamous cell carcinoma (HNSCC) that progressed after first-line therapy;3 recent results from clinical trials with immune checkpoint inhibitors have shown promising activity for secondline therapy
Results presented after long-term follow-up confirm the anti-tumour activity and tolerability of Treatment-related adverse event Any grade occurring in ≥2% of patients (No (%))
ALT alanine aminotransferase, AST aspartate aminotransferase, TSH thyroid stimulating hormone pembrolizumab in the heavily pre-treated HNSCC patient population enrolled in KEYNOTE-012
Summary
More than 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed each year. Most patients present with locally advanced disease, which is most often managed using a multi-method approach that combines surgery, chemotherapy, and radiation therapy. With disease recurrence or metastatic disease, the standard first-line treatment is the combination of cetuximab, platinum, and fluorouracil (i.e., EXTREME regimen). Historically, treatment options were limited for patients with advanced HNSCC that progressed after first-line therapy; recent results from clinical trials with immune checkpoint inhibitors have shown promising activity for secondline therapy.4–7The programmed death 1 (PD-1) pathway is an important immune checkpoint exploited by immunosuppressive cancers including HNSCC to avoid immune detection. Binding of PD-1 by either of its ligands, PD-L1 or PD-L2, suppresses the activation of effector T cells. this interaction functions to protect against excessive inflammation under normal conditions, it is hypothesised that upregulation of the PD-1 pathway allows cancer cells to develop adaptive immune resistance. Both PD-L1 and PD-L2 expression have been reported in HNSCC, and the PD-1 pathway has been established as an effective target in HNSCC. Treatment options were limited for patients with advanced HNSCC that progressed after first-line therapy; recent results from clinical trials with immune checkpoint inhibitors have shown promising activity for secondline therapy.. Binding of PD-1 by either of its ligands, PD-L1 or PD-L2, suppresses the activation of effector T cells.9–11 This interaction functions to protect against excessive inflammation under normal conditions, it is hypothesised that upregulation of the PD-1 pathway allows cancer cells to develop adaptive immune resistance.. Second-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. CONCLUSIONS: 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
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