Medication Monitor

Generic Name (Trade Name—Company)
October 14, 2015


(Keytruda—Merck & Co.)
FDA expands indication of drug for advanced non–small cell lung cancer

FDA granted accelerated approval for pembrolizumab to treat patients with metastatic non–small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express the PD-L1 protein. Pembrolizumab is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test (marketed by Dako North America Inc.), the first test designed to detect PD-L1 expression in NSCLC tumors.

Pembrolizumab targets the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, pembrolizumab may help the body’s immune system fight the cancer cells. In 2014, pembrolizumab was approved to treat patients with advanced melanoma following treatment with ipilimumab, a type of immunotherapy. Another drug, nivolumab (Opdiva—Bristol-Meyers Squibb), also targets the PD-1/PD-L1 pathway and was approved to treat squamous NSCLC in 2015.

Safety of pembrolizumab was studied in 550 patients with advanced NSCLC. Its most common adverse effects included fatigue, decreased appetite, shortness of breath or impaired breathing, and cough. Pembrolizumab  also has the potential to cause severe adverse effects that result from the immune system effect of the drug (immune-mediated adverse effects).

Effectiveness of pembrolizumab for this use was demonstrated in a subgroup of 61 patients enrolled within a larger multicenter, open-label, multipart study. The subgroup consisted of patients with advanced NSCLC that progressed following platinum-based chemotherapy or, if appropriate, targeted therapy for certain genetic mutations (ALK or EGFR). This subgroup also had PD-L1 positive tumors, as determined by the results of the 22C3 pharmDx diagnostic test.

Study participants received pembrolizumab 10 mg/kg every 2 or 3 weeks. The major outcome measure was overall response rate (percentage of patients who experienced complete and partial shrinkage of their tumors). Tumors shrank in 41% of patients treated with pembrolizumab, and the effect lasted between 2.1 and 9.1 months.                                                                                                         

In the 550 study participants with advanced NSCLC, severe immune-mediated adverse effects occurred involving the lungs, colon, and hormone-producing glands. Other uncommon immune-mediated adverse effects were rash and inflammation of blood vessels.

Women who are pregnant or breastfeeding should not take pembrolizumab because it may cause harm to a developing fetus or newborn baby. Across clinical studies, a disorder in which the body's immune system attacks part of the peripheral nervous system (Guillain-Barre Syndrome) also occurred.

FDA granted pembrolizumab breakthrough therapy designation for this indication because Merck demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies. The drug also received priority review status, which is granted to drugs that, at the time the application was submitted, have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition.

Pembrolizumab was approved under the agency’s accelerated approval program, which allows the approval of a drug to treat a serious or life-threatening disease on the basis of clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. An improvement in survival or disease-related symptoms in patients being treated with pembrolizumab has not yet been established.