The U.S. Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab) as a treatment for people with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) — the second most common form of skin cancer — that is not curable by surgery or radiation therapy.
The decision was based on data from a Phase 2 trial called KEYNOTE-629 (NCT03284424), in which Keytruda was found to reduce tumor burden in a meaningful proportion of patients. It also helped more than half of responders achieve sustained responses lasting over six months.
“In KEYNOTE-629, treatment with Keytruda resulted in clinically meaningful and durable responses,” Jonathan Cheng, MD, vice president, clinical research, Merck Research Laboratories, said in a press release.
“Today’s approval is great news for patients with cSCC and further demonstrates our commitment to bringing new treatment options to patients with advanced, difficult-to-treat cancers,” he added.
Keytruda, an immune checkpoint inhibitor developed by Merck (known as MSD outside the U.S. and Canada), works to block signals from cancer cells that prevent immune cells from effectively targeting the tumor.
It binds specifically to the PD-1 protein receptor on the surface of immune cells, preventing it from interacting with receptors (ligands) known as PD-L1 and PD-L2 on cancer cells. This allows the immune cells to recognize and eliminate the cancer cells more efficiently.
KEYNOTE-629, which is expected to run through June 2022, is investigating the safety and efficacy of Keytruda in cSCC patients whose disease returned after prior treatment (recurrent) and/or had spread to other regions in the body (metastatic).
In all, 105 individuals were included in the trial, 87% of whom had previously received at least one line of therapy, and 74% of whom had undergone prior radiation therapy. These patients could not be cured with surgery or radiation therapy. Most were white (71%), and men (76%), with a median age of 72 years (range 29–95).
Among the patients, 45% had locally recurrent disease only, meaning their cancer had returned but not yet spread to other organs. Another 24% had metastatic disease, in which the cancer had spread. A total of 31% had both recurrent and metastatic disease.
The participants received 200 mg of intravenous (into-the-vein) Keytruda every three weeks for a maximum of two years, or until they experienced signs of disease worsening or unacceptable toxicity.
Those with signs of radiographic disease progression were eligible to receive additional doses of Keytruda as long as they showed no symptoms nor a decline in performance, the disease progressed slowly, and no urgent intervention was required. Cancer lesions were evaluated every six weeks during the first year and every nine weeks during the second year.
The trial’s main goal was to determine the proportion of patients who responded to treatment — deemed as a reduction of at least 30% in target lesions. A maximum of 10 lesions were evaluated, including up to five target lesions per organ.
Secondary assessments included the duration of response, the proportion of patients with at least stable disease, time to disease progression or death, overall survival, and safety.
After a median follow-up time of 9.5 months, 34% of participants had responded to treatment. That included 4% with complete responses, or the disappearance of all target lesions, and 31% with partial responses, or at least a 30% reduction in the sum of target lesions.
At the time of the analysis, more than half of the responses were ongoing, which prevented the researchers from estimating the median duration of response. However, the duration of response ranged from 2.7 to more than 13.1 months, and 69% of responders had ongoing responses lasting at least six months. As of now, the participants have received Keytruda for a median of 5.8 months, with a range from one day to 16.1 months.
Keytruda’s safety profile was similar to that seen in prior trials testing it as a single agent for melanoma and lung cancer. Severe or life-threatening adverse events with a higher incidence than reported were low levels of lymphocytes, a type of immune cell, which happened in 11% of patients.
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