New Immunotherapy Option for Treating Metastatic Lung Cancer

The U.S. Food and Drug Administration approval means there are now three immunotherapeutics called checkpoint inhibitors approved for treating lung cancer

Use of the immunotherapeutic atezolizumab (Tecentriq) was recently expanded by the U.S. Food and Drug Association (FDA) to include the treatment of certain patients with lung cancer.

The approval means atezolizumab can now be used for treating patients with metastatic non-small cell lung cancer (NSCLC) whose disease has progressed despite treatment with a platinum-containing chemotherapy regimen and those with tumors that have EGFR or ALK genomic alterations that have progressed during treatment with an appropriate molecularly targeted therapeutic.

According to the National Cancer Institute, lung cancer is the second most commonly diagnosed cancer in the United States, with 224,390 cases expected in 2016. NSCLC accounts for about 80 to 85 percent of these cases.

The approval was based on results from two clinical trials involving a total of 1,137 patients with metastatic NSCLC. Results from the larger of these trials, the randomized phase III OAK trial, were presented at the recent European Society of Medical Oncology 2016 Annual Meeting. They showed that atezolizumab improved median overall survival by 4.2 months compared with the conventional chemotherapeutic docetaxel, which is standard of care for patients with advanced NSCLC that has progressed during or after initial chemotherapy.

These data are consistent with those from the second clinical trial, the randomized phase II POPLAR trial, which were published in The Lancet earlier this year. In this trial, atezolizumab improved median overall survival by 2.9 months compared with docetaxel.

Atezolizumab is the third member of a class of immunotherapeutics called checkpoint inhibitors to be approved for treating patients with NSCLC. The other two, nivolumab (Opdivo) and pembrolizumab (Keytruda), were approved for this use in 2015.

Each of the three checkpoint inhibitors approved for treating patients with NSCLC target the same immune checkpoint system, the PD-1?PD-L1 system. The natural function of this system is to help control the function of immune cells called T cells. However, some cancer cells exploit the system to prevent T cells from attacking them. This occurs when PD-L1, present on the surface of some cancer cells, attaches to the checkpoint protein PD-1 on T cells, slamming the brakes on the T cell’s natural cancer-fighting function.

Nivolumab and pembrolizumab target PD-1 itself, preventing the checkpoint protein from being triggered. Atezolizumab targets PD-L1, preventing it from attaching to PD-1; it also prevents PD-L1 from triggering another checkpoint protein on T cells called B7.1.

NSCLC is the second type of cancer for which the FDA has approved atezolizumab. It was first approved in May 2016 for treating certain patients with urothelial carcinoma, the most common form of bladder cancer diagnosed in the United States. Given that there are more than 90 clinical trials testing atezolizumab as a potential treatment for various types of cancer listed on clinical trials.gov, it is likely that the use of this immunotherapeutic will be expanded in the future.

The FDA approval was rendered on October 18, 2016.