The US FDA recently granted accelerated approval to Merck’s Keytruda (pembrolizumab) as a treatment for advanced (metastatic) non-small cell lung cancer (NSCLC) in patients with disease progression after other therapies have already been tried and for patients with tumors expressing the PD-L1 protein.

Keytruda is also approved for the treatment of a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test. This is the first test that detects the expression of PD-L1 in non-small cell lung tumors.

“Our growing understanding of underlying molecular pathways and how our immune system interacts with cancer is leading to important advances in medicine,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Keytruda gives physicians the ability to target specific patients who may be most likely to benefit from this drug.”

Keytruda blocks the PD-1/PD-L1 cellular pathway (immune system cells and some cancer cells proteins), and may help the immune system fight cancer cells.

The drug was approved in 2014 for the treatment of patients with a diagnosis of advanced melanoma after patients had received treatment with an immunotherapy known as ipilimumab. Bristol-Meyer Squibb’s Opdivo (nivolumab) also has a mechanism of action targeting the PD-1/PD-L1 pathway. The drug was approved this year as a treatment for patients with squamous non-small cell lung cancer (NSCLC)

Keytruda’s safety profile was evaluated in 550 patients with advanced NSCLC. The drug’s most common side effects involve decreased appetite, fatigue, cough, shortness of breath or dyspnea. The drug has been also found to cause severe immune-mediated side effects, according to the FDA.

The efficacy of the therapy was investigated in a larger multicenter, multi-part, open-label study with 61 patients with advanced NSCLC that advanced after patients received platinum-based chemotherapy or treatment of either the ALK or the EGFR genetic mutations. A patient subgroup in the study also had PD-L1 positive tumors based on the 22C3 pharmDx diagnostic test. Patients were treated with 10 mg/kg of Keytruda every two or three weeks. The study’s primary endpoint was the overall response rate. Results showed that 41% of patients who received treatment with Keytruda had their tumors shrink. These results lasted for 2.1 to 9.1 months.

In the study that involved 550 patients with a diagnosis of advanced NSCLC, the results showed that there were severe immune-mediated side effects involving the colon, the lungs and glands that produce hormones. Other adverse events included and inflammation of blood vessels (vasculitis).

Keytruda was granted breakthrough therapy designation by the FDA for NSCLC based on the fact that the study results showed that the drug offers significant clinical improvements in comparison to other available treatments. Keytruda has also received priority review status, meaning that the drug has the potential to be a significant improvement in effectiveness or safety as treatment of a serious disease.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma (SCC), and large cell carcinoma. Patients with NSCLC require a complete staging workup to evaluate the extent of disease, because stage plays a major role in determining the choice of treatment.