KEYNOTE-055 Raises Pembrolizumab Potential For Treatment-Refractory, Recurrent HNSCC

Pembrolizumab shows promise for patients with recurrent or metastatic head and neck squamous cell carcinoma who have progressed after platinum and cetuximab

medwireNews: The KEYNOTE-055 trial findings suggest that pembrolizumab may be an option for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that has proven refractory to platinum and cetuximab.

Writing in the Journal of Clinical Oncology, the investigators say the results are “consistent” with those reported for the KEYNOTE-012 study, where 18% of patients with refractory or metastatic HNSCC responded to pembrolizumab.

“The robust clinical activity demonstrated in this trial confirms the activity of this class of agents and supports ongoing immunotherapy studies in head and neck cancer”, comment lead author Joshua Bauml, from the University of Pennsylvania in Philadelphia, USA, and team.

Of the 171 heavily pretreated patients with progressive disease in the past 6 months who were given pembrolizumab 200 mg every 3 weeks for the phase II study, 82% had a combined positive score for programmed cell death ligand 1 (PD-L1) tumour expression of at least 1%, and 22% were positive for human papillomavirus (HPV).

The primary endpoint of the RECIST-measured overall response rate was 16%, with one complete response, partial responses in 16% of patients, stable disease in 19% and progressive disease in 51%.

Response was more common in patients positive for PD-L1 expression than those with negative tumours (18 vs 12%), but was comparable between HPV-positive and -negative patients (16 vs 15%).

The median duration of response was 8 months but 21 patients were continuing to respond to pembrolizumab at time of data cutoff and response at this time was at least 6 months long in eight of the group.

“Consistent with prior studies of immunotherapy in cancer, overall survival in KEYNOTE-055 was encouraging despite no apparent improvement in progression-free survival [PFS]”, comment the researchers, who believe that PFS “may not be the best outcome of interest for immunotherapy trials”.

Median PFS was 2.1 months, with just 23% of patients reaching the 6-month mark, while overall survival was a median of 8 months. Both survival outcomes were comparable in patients with and without HPV.

The KEYNOTE-055 investigators describe pembrolizumab as being “well tolerated”, with just 4% of participants discontinuing treatment because of side effects.

Treatment-related adverse events of any grade occurred in 64% of the group, but only 15% of patients had a grade 3 or more severe event and there was one death from treatment-related pneumonitis. The most common grade 3–5 events were aspartate aminotransferase increase and anaemia, affecting 2% of patients each. Immune-mediated events of any grade included hypothyroidism (16%), pneumonitis (4%) and hyperthyroidism (2%).

While acknowledging a “paucity of efficacy data” for patients with recurrent/metastatic HNSCC refractory to both platinum and cetuximab to compare their findings with, Joshua Bauml et al write that the “overall response and survival rates reported with pembrolizumab seem favorable even when compared with other treatments in patients with fewer prior therapies.”

They add: “It is particularly notable that patients in KEYNOTE-055 had prolonged responses, given that increasing lines of therapy are generally associated with worse outcomes in oncology.”


Bauml J, Seiwert TY, Pfister DG, et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: Results from a single-arm, phase II study. J Clin Oncol; Advance online publication 22 March 2017. DOI: 10.1200/JCO.2016.70.1524

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