FDA Approves Pembrolizumab for Cutaneous Squamous Cell Carcinoma

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

The recommended doses of pembrolizumab for cSCC are 200 mg every 3 weeks or 400 mg every 6 weeks.

Efficacy of pembrolizumab for this indication was investigated in the multicenter, multi-cohort, non-randomized, open-label, KEYNOTE-629 trial. Trial participants received 200 mg of pembrolizumab intravenously every 3 weeks until disease progression, unacceptable toxicity, or a maximum of 24 months. Tumor status was assessed every 6 weeks during the first year and every 9 weeks during the second year.

Notably, the trial excluded patients who had previously received therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody and those with autoimmune disease or a medical condition that required immunosuppression.

The primary outcome measures were objective response rate (ORR) and response duration as assessed by blinded independent central review according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

The ORR was 34% (95% CI, 24-44) and median response duration was not reached (range, 2.7-13.1+ months).

Adverse events (AEs) observed in patients with cSCC enrolled in KEYNOTE-629 were similar to those previously observed in patients who received pembrolizumab as a single agent in other trials. The most common AEs with pembrolizumab are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is also associated with immune-mediated AEs, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.

Notably, the efficacy and safety of pembrolizumab using a dosage of 400 mg every 6 weeks for cSCC was mainly based on the modeling of dose/exposure efficacy and safety relationships, as well as observed pharmacokinetic data in patients with melanoma.

Reference:

FDA. FDA approves pembrolizumab for cutaneous squamous cell carcinoma. FDA website. Published June 24, 2020. fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-cutaneous-squamous-cell-carcinoma. Accessed June 24, 2020.