CHICAGO—Pembrolizumab immunotherapy is effective for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), results of the KEYNOTE-012 trial presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting have shown.

At a fixed dose of 200 mg intravenously every 3 weeks, pembrolizumab “was well tolerated and demonstrated a clinically meaningful overall response rate of 24.8% in patients with recurrent/metastatic SCCHN,” reported Tanguy Y. Seiwert, MD, an assistant professor of medicine, and associate HNC program leader at The University of Chicago in Chicago, IL.

However, “it is important to note that response rate may underestimate the rate of benefit in patients, and ultimately we need to assess survival,” said Dr. Seiwert in an ASCO press release.

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“We know from other diseases where the experience with immunotherapy is larger, that patients who have disease stabilization or even initially experience disease progression upon receiving immunotherapy ultimately may derive significant benefit that can translate into longer survival.”

Pembrolizumab (MK-3475), a humanized monoclonal antibody that blocks interaction of PD-1 with its ligands, PD-L1 and PD-L2, promotes activity of tumor-specific effector T cells.

Previously, the KEYNOTE 012 study had demonstrated clinical activity of pembrolizumab 10 mg/kg every 2 weeks in patients with recurrent/metastatic SCCHN enriched for PD-L1–positive tumors. Response rate was 20%. Dr. Seiwert reported on the study’s larger SCCHN expansion cohort, irrespective of PD-L1 expression or HPV status, using a 3-weekly fixed dose.

The primary end point was overall response rate per investigator assessment (RECIST 1.1). Secondary objectives included progression-free survival and overall survival.

A total of 132 patients with recurrent/metastatic SCCHN were enrolled and evaluated every 8 weeks with radiographic imaging. Mean age was 60 years, 83.3% were male, and 37.9% had 3 or more lines of therapy for recurrent disease.

At a median follow-up of 5.7 months (range: 0.2-8.7 months), the overall response rate was 24.8%, with 7 of the 34 patients who were HPV-positive and 22 of the 81 patients who were HPV-negative responding.

Among all responders, there was one complete response and 26 partial responses. Median time to response was 9.0 weeks (range: 7.6-18 weeks). Median duration of response was not reached, he said. A total of 40 patients remain on therapy, and 86% of responding patients (25 of 29) remain in response.

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Drug-related adverse events (AEs) of any grade occurred in 59.8% of all enrolled patients; drug-related grade 3 or higher AEs occurred in 9.8% of patients.

The most common drug-related AEs (≥5%) of any grade were fatigue (15.2%), hypothyroidism (9.1%), decreased appetite (7.6%), rash (7.6%), dry skin (6.8%), pyrexia (6.8%), arthralgia (5.3%), nausea (5.3%), and decrease in weight (5.3%).

“This is yet another exciting example where PD-1 immunotherapy might work better and more reliably than existing drugs, and with fewer side effects,” said ASCO Expert Gregory A. Masters, MD, in a press release.

“The diversity of patients who responded is greater than in any previous clinical trial. But we still need larger studies and longer follow-up to assess the impact of this treatment on patient survival.”

Pembrolizumab is currently being evaluated in two phase 3 trials to investigate its clinical benefit compared with standard of care chemotherapy, Dr. Seiwart said.


  1. Seiwert TY, Haddad RI, Gupta S, et al. Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort. J Clin Oncol. 2015;33:(suppl; abstr LBA6008).