2015 American Society of Clinical Oncology Annual Meeting:

Clinically Meaningful Antitumor Activity Reported for Pembrolizumab in Advanced Squamous Cell Carcinoma of the Head and Neck

Preliminary results from a 132-patient expansion cohort of the KEYNOTE-012 study report on the antitumor activity and safety of pembrolizumab in patients with advanced squamous cell carcinoma of the head and neck were presented by Tanguy Seiwert, MD, Assistant Professor at the University of Chicago, School of Medicine in Illinois.

Checkpoint Inhibitor Pembrolizumab
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction of programmed cell death protein (PD-L1) with its ligands, PD-L1 and PD-L2, thereby promoting activity of tumor-specific effector T cells, which induce an antitumor immune response.

Larger Expansion Cohort of KEYNOTE 012
A new, larger, 132-patient expansion cohort of KEYNOTE 012 in squamous cell carcinoma of the head and neck, irrespective of biomarker status, using a 2-weekly fixed dose, was presented at the American Society of Clinical Oncology in Chicago during May 29-June 2, 2015.

Patients with advanced squamous cell carcinoma of the head and neck irrespective of PD-L1 expression or human papillomavirus status received a fixed dose of 200 mg pembrolizumab intravenously every 3 weeks. Patients were evaluated every 8 weeks with radiographic imaging.

Objectives of the KEYNOTE 012 Expansion Cohort
The primary endpoint measured were the overall response rates per investigator assessment according to Response Evaluation Criteria in Solid Tumors 1.1.

Secondary objectives included progression-free survival and overall survival. Adverse events were assessed according to Common Terminology Criteria for Adverse Events v4. PD-L1 is assessed retrospectively by immunohistochemistry.

Status of Patients Enrolled in the Expansion Cohort

  • A total of 132 patients with recurrent/metastatic squamous cell carcinoma of the head and neck were enrolled.
  • Mean age was 58.9 ± 9.7 years; 83.3% are male; and 56.8% have had at least two lines of therapy for recurrent disease.
  • Median follow-up duration was 5.7 months.

Forty patients were still on treatment at the time of the presentation. Of 132 treated patients, 117 were available for this preliminary efficacy analysis with a post-baseline scan or hade discontinued therapy prior to the scan due to clinical progression or adverse events.

Objective Response Rate of 24.8% Was Reported
Objective response rate (confirmed and unconfirmed) per Response Evaluation Criteria in Solid Tumors 1.1 was 24.8% with 28 partial responses and one complete response. Overall, 56% of patients experienced any level of tumor shrinkage.

Activity was observed in both human papillomavirus-positive patients with a response rate of 20.6% and human papillomavirus–negative patients with a response rate of 27.2%.

Responses appeared to be durable with 86% of responding patients experiencing an ongoing response at the time of data cutoff. Biomarker analysis for PD-L1 is ongoing. However, in a related abstract, a novel gamma-interferon signature from another head and neck cancer cohort has suggested feasibility and potential clinical utility of such an approach with a high negative predictive value of 95% and positive predictive value of 40%.

Pembrolizumab Was Well Tolerated
Drug-related adverse events of any grade occurred in 59.8% of enrolled patients, and drug-related grade ≥3 adverse events occurred in 9.8%.

The most common drug-related adverse events (≥5%) of any grade were fatigue (15.2%), hypothyroidism (9.1%), decreased appetite (7.6%), and rash (7.6%).

Conclusions

  • Pembrolizumab given at a fixed dose of 200 mg every 3 weeks was well tolerated and has demonstrated a clinically meaningful objective response rate of 24.8% in biomarker-unselected patients with recurrent/metastatic squamous cell carcinoma of the head and neck.
  • Pembrolizumab appears to be active in both human papillomavirus-positive as well as -negative head and neck cancers.

June 30, 2015

Next Summary:
Negative Drug Efflux Pump Expression Confers A More Favorable Outcome Than Positive Expression
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