FDA Expands Indication for Pembrolizumab in Locally Advanced CSCC

Pembrolizumab has been granted an expanded indication by the FDA for locally advanced cutaneous squamous cell carcinoma.

The FDA has granted an approval for an expanded label for the single-agent PD-1 inhibitor, pembrolizumab (Keytruda), as treatment for patients with locally advanced cutaneous squamous cell carcinoma (CSCC) that cannot be cured through surgery or radiation, according to a press release by drug developer Merck.1

The drug’s first approval in cSCC was granted on June 24, 2020. The expanded indication was based on the phase 2 KEYNOTE-629 trial (NCT03284424), wherein pembrolizumab yielded an objective response rate (ORR) of 50% (n = 54; 95% CI, 36-64), consisting of a complete response rate of 17% and a partial response rate of 33%.2 Moreover, among those who responded (n = 27), 81% and 37% experienced a duration of response (DOR) lasting 6 months or longer and 12 months or longer, respectively. Based on these findings, pembrolizumab monotherapy was granted an indication for those with locally advanced CSCC that cannot be cured through radiation or surgery.

“This approval is great news for these patients and further demonstrates Merck’s commitment to the skin cancer community. [Pembrolizumab] has shown meaningful efficacy in patients with locally advanced or recurrent or metastatic cutaneous squamous cell carcinoma that cannot be cured by surgery or radiation,” Vicki Goodman, vice president of clinical research at Merck, said in a press release. “This expanded indication reinforces the role of [pembrolizumab] in this cancer type, which is the second most common form of non-melanoma skin cancer.”

The multicenter, multi-cohort, nonrandomized, open-label trial examined the efficacy of intravenous pembrolizumab at 200 mg administered every 3 weeks until disease progression, unacceptable toxicity, or 24 months of treatment. Those who had initial radiographic disease progression could be treated with additional doses of pembrolizumab through confirmation of disease progression unless their disease was symptomatic, rapidly progressive, in need of immediate intervention, or occurred in conjunction with a decrease in performance status. Tumor status assessment occurred every 6 weeks during the first year and every 9 weeks thereafter. The agent’s is recommended for administration at doses of 200 mg every 3 weeks or 400 mg every 6 weeks for patients with CSCC.

The trial enrolled patients who had histologically-confirmed relapsed or metastatic CSCC. Patients also needed to be ineligible for surgical resection and have an ECOG performance status of 0 or 1.

The primary outcome of the study was ORR, with key secondary outcomes including DOR, disease control rate, progression-free survival, and overall survival.

Among those with locally advanced disease, patients had a median age of 76 years (range, 35-95) and 80% were 65 or older. The majority of patients were male (72%) and white (83%). In total, 41% of patients had a performance status of 0 and 59% had a status of 1. Additionally, 22% received 1 or more prior lines of therapy while 63% had underwent radiation previously.

Among the population of 159 patients with advanced CSCC, grade 3/4 laboratory abnormalities occurred at a higher incidence and included lymphopenia (10%) and decreased sodium (10%). Severe or fatal immune-mediated adverse effects can occur at any time during or after treatment with pembrolizumab and can include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and allogenic hematopoietic stem cell transplantation complications.


  1. FDA approves expanded indication for Merck’s KEYTRUDA® (pembrolizumab) in locally advanced cutaneous squamous cell carcinoma (cSCC). News release. Merck. July 6, 2021. Accessed July 6, 2021. https://bit.ly/3xo3Vet
  2. FDA approves pembrolizumab for cutaneous squamous cell carcinoma. News release. FDA. June 24, 2020. Accessed July 6, 2021. https://bit.ly/3dOqd1k
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