Pembrolizumab effective, safe for recurrent, metastatic cutaneous squamous cell carcinoma
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Pembrolizumab induced clinically meaningful and durable responses among elderly patients with recurrent or metastatic cutaneous squamous cell carcinoma, according to study results published in Journal of Clinical Oncology.
The FDA approved pembrolizumab (Keytruda, Merck) for this patient population based on these results from the single-arm, phase 2 KEYNOTE-629 trial, which also showed the agent had an acceptable safety profile.
“Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer, accounting for 20% of all skin cancer deaths,” Jean-Jacques Grob, MD, PhD, professor of dermatology at Hospital de la Timone in France, and colleagues wrote. “Mortality rates exceed 70% in patients with distant metastases, with recurrence rates from 15% to 28%. Until recently, there was no consensus on treatment recommendations for patients with unresectable, locally advanced, recurrent or metastatic cSCC.”
Researchers noted that cSCC is considered an immunogenic cancer and has a high mutational burden, which may be accounted for by long-term sun exposure leading to DNA damage. Additionally, a positive correlation exists between PD-L1 expression in patients with cSCC and pathologic findings related to metastatic risk, suggesting the disease will respond to immune checkpoint inhibitors such as the PD-1 inhibitor pembrolizumab.
The open-label KEYNOTE-629 trial included 105 patients (median age, 72 years; 80% men) with relapsed and/or metastatic cSCC ineligible for surgery or radiation. Patients received pembrolizumab dosed at 200 mg every 3 weeks for about 2 years until disease progression or unacceptable toxicity.
Objective response rate served as the primary endpoint. Duration of response, disease control rate, PFS, OS and safety served as secondary endpoints.
Median follow-up was 11.4 months (range, 0.4-16.3).
Results showed an ORR of 34.3% (95% CI, 25.3-44.2), including four complete responses and 32 partial responses, and a disease control rate of 52.4% (95% CI, 42.4-62.2).
Median duration of response was not reached (range, 2.7-13.1+). Median PFS was 6.9 months (95% CI, 3.1-8.5) and 32.4% of patients remained progression free at 12 months. Median OS had not been reached (95% CI, 10.7-not reached) and 60.3% of patients remained alive at 12 months.
Treatment-related adverse events occurred in 66.7% of patients, with the most common being pruritus (14.3%), asthenia (13.3%) and fatigue (12.4%).
Six patients (5.7%) experienced grade 3 to grade 5 treatment-related adverse events. One patient died of treatment-related cranial nerve neuropathy.
“Overall, pembrolizumab provides a therapeutic benet and offers an effective treatment option for patients with recurrent and/or metastatic cSCC,” Grob and colleagues wrote. “The observations in this phase 2 trial highlight the role of pembrolizumab monotherapy as an attractive treatment option in this patient population.”
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