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ASCO 2015: Pembrolizumab Produces Clinically Meaningful Response in Patients With Recurrent or Metastatic Head and Neck Cancer

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Key Points

  • Pembrolizumab produced a clinically meaningful overall response rate in a study of 132 patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
  • The overall objective response rate was 24.8%, including 26.3% in HPV-negative patients and 20.6% in HPV-positive patients.
  • 57% of patients experienced some tumor shrinkage.
  • Pembrolizumab was well tolerated, with serious side effects occurring in less than 10% of patients.

Immunotherapy with pembrolizumab (Keytruda) produced a clinically meaningful overall response rate in a study among 132 patients with recurrent or metastatic squamous cell carcinoma of the head and neck. The overall objective response rate was 24.8%, and 57% of patients experienced some tumor shrinkage, according to results announced at a press conference at the 2015 ASCO Annual Meeting in Chicago (Abstract LBA6008).

Pembrolizumab is a humanized monoclonal antibody that blocks interaction of PD-1 with its ligands PD-L1 and PD-L2 to promote activity of tumor-specific effector T cells.

“The efficacy we saw was remarkable—pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy cetuximab [Erbitux],” said lead study author Tanguy Seiwert, MD, Assistant Professor of Medicine and Associate Program Leader for Head and Neck Cancer at the University of Chicago. “We have high hopes that immunotherapy will change the way we treat head and neck cancer,” Dr. Seiwert stated. Dr. Seiwert will present more detailed results at the head and neck cancer session on Monday, June 1.

Response Rate May Underestimate Benefit

“Unlike EGFR inhibitors, where data at this meeting suggest potentially less efficacy in HPV-positive tumors, pembrolizumab showed similar levels of activity in both HPV-positive and HPV-negative tumors,” Dr. Seiwert continued. (The objective response rate was 26.3% in HPV-negative patients and 20.6% in HPV-positive patients).

“Importantly those patients that did respond, oftentimes continue to have responses,” with 86% of responding patients remaining in response, Dr. Seiwert reported at the press conference. “In addition to the 25% response rate, about 25% of patients had stable disease,” he added. “So when we take this together, the disease control rate is about 50%, which is remarkable for this disease, especially in a heavily treated population.”

“It is important to note that response rate may underestimate the rate of benefit in patients, and ultimately we need to assess survival. 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,” according to Dr. Seiwert.

Expansion Cohort of KEYNOTE-012

The study results are from an expansion cohort of the KEYNOTE-012 trial, which had previously demonstrated clinical activity of pembrolizumab when used in patients with recurrent/metastatic squamous cell carcinoma of the head and neck enriched for PD-L1 positive tumors. The expansion cohort included patients with advanced squamous cell carcinoma of the head and neck irrespective of PD-L1 expression or HPV status.

These patients received a fixed dose of pembrolizumab of 200 mg given as an infusion every 3 weeks. More than half (59%) had received two or more lines of prior therapy. The mean age of the study participants was 58.9 years, and 83.3% were male.

Less Than 10% Had Serious Side Effects

Pembrolizumab was well tolerated, with serious side effects occurring in less than 10% of patients. The most common side effects were fatigue, rash, and itching. More serious immune-related side effects such as pneumonitis and colitis were observed in a small number of patients. “This was certainly better tolerated than what we usually use in head and neck cancer, which is aggressive chemotherapy,” Dr. Seiwert pointed out.

“This is yet another exciting example where PD-1 immunotherapy might work better and more reliably than existing drugs, and with fewer side effects,” according to ASCO Expert Gregory A. Masters, MD, FACP, FASCO. “The diversity of patients who responded is greater than in any previous clinical trials. But we still need larger studies and longer follow-up to assess the impact of this treatment on patient survival.” Dr. Masters is an attending physician at the Helen F. Graham Cancer Center, Newark, Delaware, and serves as an Associate Professor at the Thomas Jefferson University Medical School.

Two ongoing phase III studies are evaluating pembrolizumab vs standard treatment in patients with recurrent/metastatic head and neck cancer.

This study received funding from Merck Sharp & Dohme Corp. Dr. Seiwert reported honoraria from Novartis, Bayer/Onyx, and Merck; and research funding (institutional) from Genentech/Roche and Boehringer Ingelheim.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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