On July 6, the U.S. Food and Drug Administration (FDA) approved an expanded label for pembrolizumab, an anti–PD-1 agent, as monotherapy for patients with locally advanced cutaneous squamous cell carcinoma that is not curable by surgery or radiation. This approval is based on data from the second interim analysis of the phase II KEYNOTE-629 trial.
More on KEYNOTE-629
KEYNOTE-629 (ClinicalTrials.gov identifier: NCT03284424) is a multicenter, multicohort, nonrandomized, open-label trial that enrolled patients with recurrent or metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma. The trial excluded patients with autoimmune disease or a medical condition that required immunosuppression.
Patients received pembrolizumab at 200 mg intravenously every 3 weeks until documented disease progression, unacceptable toxicity, or a maximum of 24 months. Patients with initial radiographic disease progression could receive additional doses of pembrolizumab during confirmation of progression unless disease progression was symptomatic, rapidly progressive, required urgent intervention, or occurred with a decline in performance status.
Assessment of tumor status was performed every 6 weeks during the first year and every 9 weeks during the second year. The major efficacy outcome measures were objective response rate and duration of response as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Among the 54 patients treated, the study population characteristics were: a median age of 76 years (range = 35–95), 80% age 65 or older; 72% male; 83% White and 13% race unknown; 41% Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 and 59% ECOG PS of 1. Twenty-two percent of patients had received one or more prior lines of therapy; 63% received prior radiation therapy.
The objective response rate was 50% (95% confidence interval [CI] = 36%–64%), including a complete response rate of 17% and a partial response rate of 33%, for patients treated with pembrolizumab. After a median follow-up of 13.4 months, the median duration of response had not yet been reached (range = 1.0+ to 17.2+ months). Among the 27 responding patients, 81% had a duration of response of 6 months or longer, and 37% had a duration of response of 12 months or longer.
Among the 159 patients with advanced cutaneous squamous cell carcinoma (recurrent or metastatic or locally advanced disease) enrolled in KEYNOTE-629, the median duration of exposure to pembrolizumab was 6.9 months (range = 1 day–28.9 months).
Adverse reactions occurring in patients with recurrent or metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma were similar to those occurring in 2,799 patients with melanoma or non–small cell lung cancer treated with pembrolizumab as a single agent. Laboratory abnormalities (grades 3 and 4) that occurred at a higher incidence included lymphopenia (10%) and decreased sodium (10%).