On 24 June 2020, the US FDA (United States Food and Drug Administration) granted its approval to pembrolizumab (KEYTRUDA) for patients having recurrent or metastatic cSCC (cutaneous squamous cell carcinoma) that is not curable by surgery or radiation. A multicentre, multi-cohort, non-randomized, open-label trial (KEYNOTE-629) was conducted to explore the efficacy of pembrolizumab.
Notably, those individuals that had previously received therapy with an anti-PD-1 (Programmed cell death protein-1), anti-PD-L1, or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) antibody and those with autoimmune disease or a medical condition requiring immunosuppression were excluded from this study.
The enrolled participants received an intravenous infusion of 200 mg pembrolizumab every 3 weeks until unacceptable toxicity, disease progression, or a maximum of 24 months. Every six weeks during the first year and every nine weeks during the second year, the tumor status of patients was precisely examined.
The ORR (objective response rate) and response duration as assessed by blinded independent central review according to RECIST (Response Evaluation Criteria in Solid Tumors) guidelines (version 1.1), modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ were the primary outcome measures.
The median response duration was not attained (range: 2.7, 13.1+ months) and the ORR was illustrated to be 34%. In patients with cSCC, the occurrence of toxic reactions was found to be comparable to those occurring in patients treated with pembrolizumab as a single agent in other clinical trials.
The major toxic effects linked with pembrolizumab administration are musculoskeletal pain, fatigue, decreased appetite, diarrhea, nausea, pyrexia, cough, rash, constipation, dyspnoea, pain, abdominal pain, and pruritus. Pembrolizumab is also linked with immune-mediated toxic effects such as colitis, pneumonitis, hepatitis, endocrinopathies, skin adverse reactions, and nephritis.
Notably, for managing cSCC, the safety and efficacy of pembrolizumab utilizing a dosage of 400 mg every six weeks were substantially in accordance with the modelling of dose/exposure safety and efficacy relationships, as well as pharmacokinetic data witnessed in patients suffering from melanoma. For managing cSCC, the dose of pembrolizumab is recommended to be 200 mg every 3 weeks or 400 mg every 6 weeks.
Source: US FDA
Original title of the article FDA approves pembrolizumab for cutaneous squamous cell carcinomaAuthors: