FDA approves Keytruda for advanced melanoma

September 5, 2014

FDA has approved pembrolizumab (Keytruda, Merck) for treatment of patients with advanced or unresetable melanoma who are no longer responding to other drugs.

FDA has approved pembrolizumab (Keytruda, Merck) for treatment of patients with advanced or unresetable melanoma who are no longer responding to other drugs.

According to the American Melanoma Foundation, more than 73% of skin cancer deaths are from melanoma. Advanced melanoma spreads to internal organs and may result in death. One person per hour dies from melanoma.

Keytruda is given to patients at a dose of 2 mg/kg every 3 weeks for use following treatment with ipilimumab, a type of immunotherapy. For melanoma patients whose tumors express a gene mutation called BRAF V600, Keytruda is intended for use after treatment with ipilimumab and a BRAF inhibitor, a therapy that blocks activity of BRAF gene mutations.

This is the first FDA-approved anti-PD-1 therapy for any cancer. PD-1 restricts the body’s immune system from attacking melanoma cells.

“This drug will be used frequently in metastatic melanoma patients,” according to Geoffrey Gibney, MD, a medical oncologist in the department of cutaneous oncology at Moffitt Cancer Center. “A majority of patients will ultimately progress after management with frontline drugs [ipilimumab/BRAF-targeted agents] and be eligible for treatment with pembrolizumab.”  

Keytruda received breakthrough therapy designation for advanced melanoma. It is the sixth new melanoma treatment approved since 2011. The 5 prior FDA approvals for melanoma include: ipilimumab (2011), peginterferon alfa-2b (2011), vemurafenib (2011), dabrafenib (2013), and trametinib (2013).

Clinical trials of pembrolizumab have demonstrated objective responses in approximately 25% to 40% of metastatic melanoma patients, according to Dr Gibney.

Keytruda’s efficacy was established in 173 clinical trial participants with advanced melanoma whose disease progressed after prior treatment. All participants were treated with Keytruda, either at the recommended dose of 2 mg/kg or at a higher dose of 10 mg/kg. In half of the participants who received Keytruda at the recommended dose of 2 mg/kg, approximately 24% had their tumors shrink. This effect lasted at least 1.4 to 8.5 months and continued beyond this period in most patients. A similar percentage of patients had their tumor shrink at the 10 mg/kg dose.

Keytruda’s safety was established in the trial population of 411 participants with advanced melanoma. Fatigue, cough, nausea, itchy skin (pruritus), rash, decreased appetite, constipation, joint pain (arthralgia) and diarrhea were the most common side effects. Keytruda also has the potential for severe immune-mediated side effects. In the 411 participants with advanced melanoma, severe immune-mediated side effects involving healthy organs, including the lung, colon, hormone-producing glands and liver, occurred uncommonly.