Cancer Treatment Today

Keytruda )pembrolizumab) is now FDA approved for head and neck cancer in 2nd line.  Immunotherapy with the anti-PD-1 antibody pembrolizumab (Keytruda®) was effective in one out of four patients with recurrent or metastatic head and neck cancer, according to results presented at the 2015 meeting of the American Society for Clinical Oncology (ASCO). The KEYNOTE-012 expansion cohort study included 132 patients with recurrent or metastatic SCCHN who were assigned to receive 200 mg of pembrolizumab every 3 weeks regardless of PD-ligand 1 (L1) expression or human papillomavirus (HPV) status. The primary endpoint of the study was overall response rate.

Evaluating 117 patients, the overall response rate was 24.8%, indicating that about one in four patients responded. The response rate was 20.6% in patients with HPV-positive disease and 27.2% in patients with HPV-negative disease, showing that the drug is active in both entities. In addition, 24.8% of patients in the trial had stable disease. Combined, this translated into a disease control rate of about 50%, and 56% of patients had a decrease in the size of tumor lesions.

In another trial using Pembrolizumab 10 mg/kg was given every 2 weeks. The ORR (confirmed and unconfirmed) per RECIST v1.1 by investigator review was 20%, and response duration ranged from 8+ to 41+ weeks (median not reached). Nine of 11 responders had a smaller target lesion burden at baseline. The ORR was similar in HPV-positive and HPV-negative patients, whereas PFS and OS were longer in HPV-positive patients. PD-L1 expression was positively correlated with ORR (p = 0.018) and PFS (p = 0.024). The ORR was 50% in the 12 patients with high PD-L1 expression. However, drug-related adverse events of any grade occurred in 58% of patients (grade 3 in 17%). The most common drug-related adverse events were fatigue (18%), pruritus (10%), and nausea (8%). There were no drug-related deaths.

Based on this data, the drug was FDA approved. KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy [see Clinical Studies].

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

1. Seiwert, TY, Burtness, B, Mehra, R, Weiss, J, Berger, R, Eder, JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial [published online ahead of print May 27, 2016]. Lancet Oncol.

2.Raffaele Addeo et al,  Editorial Pembrolizumab: the value of PDL1 biomarker in head and neck cancer Expert Opinion, Published online: 21 Jul 2016 http://www.tandfonline.com/doi/full/10.1080/14712598.2016.1211635

3.NCCN, Head and Neck 2018