FDA Approves Pembrolizumab for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma

Pembrolizumab received FDA approval for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma that cannot be cured by either surgery or radiation.

The FDA has granted approval to pembrolizumab (Keytruda), a PD-1 checkpoint inhibitor, for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma that cannot be cured by either surgery or radiation.1

This approval is based on findings from the phase 2 KEYNOTE-629 clinical trial (NCT03284424), which evaluated a 200-mg dose of pembrolizumab administered intravenously every 3 weeks until disease progression, unacceptable toxicity, or a maximum of 24 months. The study excluded patients who had received prior anti–PD-1, anti–PD-L1, or anti–CTLA-4 antibody therapy, as well as patients with an autoimmune disease or a medical condition that requires immunosuppression.

The objective response rate (ORR), which was the primary end point of the study, with pembrolizumab was 34.3% (95% CI, 25.3%-44.2%), and the median duration of response was not reached (range, 2.7-13.1+ months).1 Four patients had a complete response (3.8%; 95% CI, 1.0%-9.5%), and 32 patients had achieved a partial response (30.5%; 95% CI, 21.9%-40.2%) out of 105 treated patients. The disease control rate was 52.4% (95% CI, 42.4%-62.2%).2

After achieving a response, 31 patients had a minimum follow-up of 6 months and 7 had a minimum follow-up of 12 months. Responses remained ongoing in 25 (79.5%) of the patients who were followed for 6 months and 1 (65.6%) in the group that had longer follow-up.

The median progression-free survival was 6.9 months (95% CI, 3.1-8.5), and the 12-month progression-free survival rate was 32.4%. The median overall survival had not yet been reached (95% CI, 10.7-not reached), but the 12-month overall survival rate was 60.3%.

The toxicities observed with pembrolizumab in the KEYNOTE-629 trial appeared similar to those of patients receiving pembrolizumab as a single agent in other studies. The most common adverse events (AEs) were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. The agent is also associated with immune-mediated AEs, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.1

Treatment-emergent AEs were observed in 70 patients (66.7%), and 6 patients experienced these events of grade 3 severity or greater. One patient died due to treatment-related cranial nerve neuropathy.2

KEYNOTE-629 is a multicenter, multi-cohort, nonrandomized, open-label study. To be eligible for participation in the trial, patients had to be at least 18 years old, have locally advanced cutaneous squamous cell carcinoma, and be ineligible for surgical resection or radiotherapy. Patients must also have had measurable disease by RECIST v1.1 criteria and an ECOG performance status of 0 or 1.1

Responses to treatment were assessed by imaging 6 weeks after the initiation of pembrolizumab and every 6 weeks thereafter through year 1, and every 9 weeks after that, or more frequently if clinically indicated. Patients were followed up after disease progression or the start of a new anticancer therapy every 12 weeks until death, withdrawal of consent, or completion of the study.

Safety was monitored throughout the study and for 30 days following the completion of treatment of 90 days if the patient experienced serious toxicities. Secondary end points of the study included duration of response, disease control rate, progression-free survival, overall survival, AEs, and treatment discontinuations due to AEs.

For the cutaneous squamous cell carcinoma indication, the recommended doses for pembrolizumab are 200 mg every 3 weeks or 400 mg every 6 weeks.


1. FDA approves pembrolizumab for cutaneous squamous cell carcinoma. News release. FDA. June 24, 2020. Accessed June 24, 2020. https://bit.ly/2A5M6so

2. Grob JJ, Mendoza RG, Basset-Seguin N, et al. LBA72 - Pembrolizumab for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC): Efficacy and safety results from the phase II KEYNOTE-629 study. Presented at the European Society of Medical Oncology Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA72.

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