FDA Approves Pembrolizumab for Cutaneous Squamous Cell Carcinoma

The FDA has approved pembrolizumab (Keytruda) for patients with either recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Efficacy of the agent was investigated in the multicenter, multicohort, open-label KEYNOTE-629 trial (NCT03284424). In the trial, patients who had received previous therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody were excluded, as were those with autoimmune disease or a medical condition that required immunosuppression.

In the trial, patients were administered intravenous pembrolizumab at 200 mg every 3 weeks until progressive disease, unacceptable toxicity, or they reached a maximum of 24 months on the treatment. Tumor status assessment was done every 6 weeks during the first year of treatment and then every 9 weeks during the second year.

The major efficacy outcome measures of the trial included objective response rate (ORR) and response duration per blinded independent central review in accordance with RECIST 1.1 criteria, which were modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Results showed an ORR of 34% (95% CI, 24-44) with pembrolizumab. Furthermore, the median response duration had not yet been reached (range, 2.7-13.1+ months).

With regard to safety, adverse events (AEs) reported in trial participants were comparable to those observed in patients who received the immunotherapy as a monotherapy in previous clinical trials. The most common AEs reported included fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

The agent is also known to be correlated with immune-mediated toxicities, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.

Safety and efficacy of the agent using a dose of 400 mg every 6 weeks for patients with cSCC was mostly based on modeling of dose and exposure efficacy, as well as safety relationships and observed phramcokinetic data that had been reported in patients with melanoma.