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FDA Expands Keytruda Label to Include Patients with Head-and-Neck Squamous Cell Carcinoma

Monoclonal antibody is administered every three weeks

The FDA has given the green light to pembrolizumab (Keytruda, Merck), an anti-programmed death receptor-1 (PD-1) therapy, at a fixed dose of 200 mg administered every three weeks for the treatment of patients with recurrent or metastatic head-and-neck squamous cell carcinoma (HNSCC) with disease progression during or after platinum-containing chemotherapy.

Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.

The accelerated FDA approval was based on results from a nonrandomized, open-label, phase 1b study, KEYNOTE-012, which evaluated the treatment’s safety in 192 patients with recurrent or metastatic HNSCC and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1. Efficacy was evaluated in 174 of these patients who had disease progression during or after platinum-containing chemotherapy administered for recurrent or metastatic HNSCC or after platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy. KEYNOTE-012 was the first clinical study to investigate the role of a PD-1 inhibitor in patients with recurrent or metastatic HNSCC with disease progression during or after platinum-containing chemotherapy.

Patients were enrolled into the KEYNOTE-012 trial regardless of tumor human papillomavirus (HPV) status (33% were HPV positive). The median number of prior lines of therapy administered for the treatment of HNSCC was two. Nearly all (95%) of the patients had received prior radiation therapy. A total of 174 patients were treated with pembrolizumab at a dose of 10 mg/kg every two weeks (n = 53) or a 200-mg fixed dose every three weeks (n = 121) until unacceptable toxicity or disease progression occurred. Patients without disease progression were treated for up to 24 months. Treatment with pembrolizumab could be reinitiated for subsequent disease progression and administered for up to one additional year. The primary efficacy outcome measures were the objective response rate (ORR), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1., and the duration of response.

An efficacy analysis showed an ORR of 16%, with a complete response rate of 5%. The median follow-up period was 8.9 months. Among the 28 responding patients, the median duration of response had not been reached (range, 2.4 to 27.7 months), with 23 patients showing responses of six months or longer. The ORR and duration of response were similar irrespective of the dosage regimen (10 mg/kg every two weeks or 200 mg every three weeks) or the patient’s HPV status.

Immune-mediated adverse events associated with pembrolizumab included pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, pembrolizumab should be withheld or discontinued and corticosteroids administered. Based on its mechanism of action, pembrolizumab can cause fetal harm when administered to a pregnant woman.

Pembrolizumab is now indicated for the treatment of patients with:

  • Unresectable or metastatic melanoma
  • Metastatic non–small-cell lung cancer (NSCLC) whose tumors express PD-L1
  • Recurrent or metastatic HNSCC with disease progression during or after platinum-containing chemotherapy

Sources: Merck; August 8, 2016; and Keytruda Prescribing Information; August 2016.

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