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Pembrolizumab Demonstrates "Remarkable Efficacy" in Advanced HNSCC

Lauren M. Green @OncNurseEditor
Published: Friday, May 29, 2015

Tanguy Seiwert, MD

Tanguy Seiwert, MD

In a multisite study offering the largest experience to date of how immunotherapy can be deployed in patients with head and neck cancer, the anti-PD-1 antibody pembrolizumab produced broad and durable responses in patients with advanced disease.

Fifty-six percent of patients in the study experienced some tumor shrinkage with pembrolizumab, and 86% of patients continued to respond to treatment at data cutoff March 23, 2015. Overall, pembrolizumab produced an overall response rate (ORR) of 25%, and it proved active in both HPV-positive and HPV-negative patients.

“The efficacy was remarkable—pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy, cetuximab,” said Tanguy Seiwert, MD, an assistant professor of medicine and associate leader of the head and neck cancer program at the University of Chicago, who presented the results in a press briefing May 29 at the 2015 ASCO Annual Meeting. “We have high hopes that immunotherapy will change the way we treat head and neck cancer.”

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has a poor prognosis with a median overall survival (OS) of only 13 months in patients treated in the first-line setting and 6 months in previously treated patients—the majority of patients in this study, which builds on earlier findings from the KEYNOTE-012 study (NCT01848834). In that study, pembrolizumab administered at 10 mg/kg every 2 weeks, had a 20% response rate in patients with advanced HNSCC whose tumors were PD-L1–positive.

Findings of the study reported here are from an expansion cohort involving 132 advanced HNSCC patients who were recruited regardless of their PD-L1 or HPV status. Importantly, said Seiwert, patients in this cohort received a fixed dose of pembrolizumab (200 mg/every 3 weeks), representing “a very convenient dosing schedule.”

Eligible patients had measureable disease based on RECIST 1.1 and an ECOG performance status of 0 or 1. The majority of enrollees were male (83%), and 56.8% had received ≥2 lines of therapy for disease recurrence. Radiographic imaging was used to assess tumor response every 8 weeks. Patients were treated as long as they didn’t show progression of disease or as long as they demonstrated clinical improvement, Seiwert explained.

Of 117 evaluable patients, 29 patients (24.8%; [95% CI, 17.3–33.6]) responded to treatment with pembrolizumab. For patients with HPV-positive HNSCC, the ORR was 20.6%, and in the HPV-negative cohort, ORR was 27.2%.

“In addition to the 25% response rate,” said Seiwert, “about 25% also had stable disease, so when we take these together, we have a disease control rate of about 50%, which is remarkable in this disease, especially in a heavily pretreated population.”

Moreover, he said, about two-thirds of patients had received two or more prior lines of therapy, which generally is an indicator of a very poor prognosis.

For the 56% of patients whose tumors decreased in size, Seiwert said the responses often occurred early at 8 or 16 weeks, although there were a few outliers with late responses.

“Importantly, those patients who did respond oftentimes continued to have responses—86% of patients had durable responses in this cohort,” he continued, adding that not only are responders remaining on the therapy, but many patients who have stable disease, with a total of 40 patients staying on the drug.

“Overall, and in keeping with what we already know about pembrolizumab, this was a very well-tolerated agent,” said Seiwert, “certainly better tolerated than what we usually see in head and neck cancer with aggressive chemotherapy and radiotherapy.”

Serious side effects were reported in fewer than 10% of patients. The most common side effects were fatigue (15.2% of patients), hypothyroidism (9.1%), and decreased appetite and rash, each occurring in 7.6% of patients. Four patients discontinued treatment due to immune-related AEs: two due to grade 2 interstitial lung disease and grade 3 colitis, respectively, and two patients for grade 3 pneumonitis.

Analysis of the findings based on biomarker status is ongoing, and Seiwert is hopeful that with the emergence of new potential biomarkers, researchers will be able to pinpoint which patients with HNSCC are most likely to benefit from the immunotherapy.

For example, another related study Seiwert and colleagues are reporting at ASCO (abstract 6017) has shown that the expression of the gene signature interferon-gamma in head and neck tumors had a very strong negative predictive value of response to pembrolizumab. “In the future, these results may help us, if validated, to determine which patients should or should not [be given] pembrolizumab.”

Pembrolizumab versus standard treatment for HNSCC also is being evaluated in two phase III trials that are currently recruiting participants (NCT02252042 and NCT02358031).


Seiwert TY, Haddad RI, Gupta S, et al. Antitumor activity of the anti-PD-1 antibody pembrolizumab in biomarker-unselected patients with R/M head and neck cancer: preliminary results from the KEYNOTE-012 expansion cohort. J Clin Oncol. 2015;(suppl; abstr LBA6008).

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