Immune Checkpoint Blockade Hope For SCCHN Patients

Patients with advanced squamous cell carcinoma of the head and neck may respond to pembrolizumab therapy

medwireNews: Treatment with the immune checkpoint inhibitor pembrolizumab is well tolerated and elicits a response in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), shows research published in The Lancet Oncology.

Describing the anticancer activity of the programmed death 1 (PD-1) inhibitor as “substantial and clinically significant”, the researchers believe that pembrolizumab “might represent a new treatment approach” for this patient population, whose therapeutic options are currently limited.

The SCCHN cohort of the phase Ib KEYNOTE-012 trial included 60 patients with at least 1% PD-L1 expression in tumour cells or stroma, the majority of whom had received at least one previous line of treatment for recurrent or metastatic disease. Enrolled participants were given open-label intravenous pembrolizumab 10 mg/kg every 2 weeks for up to 24 months.

Treatment-related adverse events of grade 3 or worse were observed in 17% of patients, with grade 3 alanine aminotransferase and aspartate aminotransferase increases and hyponatraemia the most common (occurring in two patients each).

Twenty percent of participants had a toxicity-related treatment interruption and 13% discontinued the study drug as a result of an adverse event. But neither of the two on-study mortalities was attributed to study treatment.

Among 45 evaluable patients, 18% achieved an overall response, defined as a complete or partial response by RECIST v1.1, as assessed by independent review.

Response to pembrolizumab was independent of human papilloma virus (HPV) status, with overall responses observed in a similar proportion of HPV-positive and HPV-negative patients, at 25% of 16 and 14% of 29, respectively, report Tanguy Seiwert, from University of Chicago Medical Center in Illinois, USA, and co-authors.

Progression-free and overall survival were a median of 2.0 and 13.0 months, respectively, with a median duration of response of 12.2 months.

In a related comment, Jean-Pascal Machiels and Pierre Coulie, from Université catholique de Louvain in Brussels, Belgium, highlight a plateau in the progression-free survival curve, which they say suggests that 20% to 30% of participants derived a benefit for over 6 months.

“This result, although a secondary endpoint, is remarkable because long-term responders with this disease are rarely seen with other systemic drugs”, they write.

These findings, along with the preliminary results from a trial of another anti-PD-1 drug nivolumab, confirm the activity of PD-1 blockade in this malignancy, say the commentators.


Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016; Advance online publication 27 May. doi:  

Machiels J-PH, Coulie PG. The promise of immunostimulatory antibodies in head and neck cancer. Lancet Oncol 2016; Advance online publication 27 May. doi:

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