Fixed-Dose Pembrolizumab ‘Tolerable’ For Advanced HNSCC

Patients with heavily pretreated, recurrent or metastatic head and neck squamous cell carcinoma may benefit from a fixed 3-weekly dose of pembrolizumab

medwireNews: A fixed low-dose pembrolizumab regimen is well tolerated and shows efficacy for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), suggest results from an expansion cohort of the KEYNOTE-012 trial.

The phase Ib study assessed the safety and efficacy of the programmed cell death protein 1 (PD-1) inhibitor when given in a 200 mg dose every 3 weeks to 132 patients unselected by human papillomavirus (HPV) status or programmed cell death ligand 1 (PD-L1) expression, 57% of whom had received at least two prior lines of treatment for recurrent or metastatic disease.

Treatment-related adverse events occurred in 62% of the patients, with grade 3 or 4 events in 6% and 3% of patients, respectively. These included immune-related adverse events in 20% of patients, with grade 3 pneumonitis in two patients, one case each of grade 3 diabetes mellitus, decubitus ulcer, colitis and drug-induced liver injury, and one incidence of grade 4 diabetic ketoacidosis.

Overall, 6% of patients discontinued pembrolizumab because of treatment-related adverse events and 22% had one or more dose interruptions, report Laura Chow, from the University of Washington in Seattle, USA, and co-workers.

After a median of 9 months, the RECIST overall response rate (ORR) was 18%, including a complete response in 3%, partial response in 15% and stable disease in 20%. The rate differed in patients with human papillomavirus (HPV)-associated and non-HPV associated disease, at 32% of 28 patients versus 14% of 104 patients.

But the ORR in the non-HPV-associated HNSCC patients is consistent with that in the original KEYNOTE-012 groups, the researchers write in the Journal of Clinical Oncology, suggesting that this population with a “particularly poor prognosis” may benefit from pembrolizumab therapy.

The median time to response was 2 months and the median duration of response was not reached, ranging from 2 months to over 11 months, and continuing at time of analysis in 83% of 24 patients with a radiological response.

Median progression-free survival (PFS) was 2 months, with a 6-month rate of 23% and varying from 37% in HPV-associated to 20% in non-HPV-associated patients. The corresponding overall survival (OS) values were 8 months, 59%, 70% and 56%.

Response did not significantly differ between patients with PD-L1 expression in at least 1% of tumour cells and those with expression in less than 1% but when immune cells were included in the analysis, there was significant difference between the groups, with an ORR of 22% versus 4%.

Both PFS and OS were significantly predicted by PD-L1 expression in tumour plus immune cells, with median OS of 303 versus 151 days for those with 1% or higher expression versus lower expression.

“Results from the current study indicate that the less frequent, fixed dose of pembrolizumab is tolerable and provides comparable antitumor activity with pembrolizumab administered in a body weight–based dosing regimen”, summarise Laura Chow and co-authors.

They conclude: “These findings support ongoing phase II (KEYNOTE-055) and phase III (KEYNOTE-040 and KEYNOTE-048) studies of the fixed-dose regimen in patients with advanced HNSCC.”


Chow LQM, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results from the phase Ib, KEYNOTE-012 expansion cohort. J Clin Oncol; Advance online publication 19 September 2016. doi: 10.1200/JCO.2016.68.1478

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