FDA Grants Accelerated Approval to Pembrolizumab for Advanced NSCLC

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The U.S. Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) to treat patients with metastatic non–small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express programmed cell death-ligand 1 (PD-L1). Pembrolizumab is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, the first test designed to detect PD-L1 expression in non–small cell lung tumors.

Pembrolizumab works by targeting the cellular pathway PD-1/PD-L1. By blocking this pathway, it 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 (Yervoy). Another drug, nivolumab (Opdivo), also targets the PD-1/PD-L1 pathway and was approved to treat squamous NSCLC in 2015.

Study Details

The safety of pembrolizumab was studied in 550 patients with advanced NSCLC. The most common side effects of pembrolizumab included fatigue, decreased appetite, dyspnea, and cough. Pembrolizumab also has the potential to cause severe immune-mediated side effects.

The 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 based on the results of the 22C3 pharmDx diagnostic test. Study participants received 10 mg/kg of pembrolizumab every 2 or 3 weeks.

The major outcome measure was overall response rate. 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 side effects occurred involving the lungs, colon, and hormone-producing glands. Other uncommon immune-mediated side effects were rash and vasculitis. 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, Guillain-Barré syndrome has also occurred.

Pembrolizumab also received priority review status and was approved under the Agency’s accelerated approval program. An improvement in survival or disease-related symptoms in patients being treated with pembrolizumab has not yet been established.  ■


1. Soria JC, et al: Efficacy and safety of pembrolizumab for patients with previously treated advanced non–small cell lung cancer enrolled in KEYNOTE-001. 2015 European Cancer Congress. Abstract 33LBA. Presented September 28, 2015.