Expanding Immunotherapy to Cervical Cancer

The FDA has expanded the use of the immunotherapeutic pembrolizumab to treat certain patients with cervical cancer.

Image via NCI/Winship Cancer Institute of Emory University

The U.S. Food and Drug Administration (FDA) recently approved pembrolizumab (Keytruda) as a treatment option for patients with recurrent or metastatic cervical cancer that tests positive for PD-L1 and that has progressed despite treatment with cytotoxic chemotherapy.

How Does Pembrolizumab Work?

Pembrolizumab is a type of immunotherapeutic known as a checkpoint inhibitor. Its development was built upon decades of basic research in the fields of immunology and cancer biology. Among the pivotal research milestones were the discoveries that immune cells called T cells are naturally capable of destroying cancer cells and that some cancers evade T cell destruction by triggering brakes called checkpoint proteins on T cells, which prevents the T cells from attacking.

Pembrolizumab targets a checkpoint protein called PD-1. The brake function of PD-1 is triggered when a protein called PD-L1, which is expressed at high levels in some tumors, attaches to it. Pembrolizumab attaches to PD-1 in a way that does not trigger its brake function. It also prevents PD-L1 and other proteins from attaching to it and triggering its brake function. Thus, pembrolizumab frees T cells to carry out their natural functions, including destroying cancer cells.

Cervical cancer incidence and death rates have been falling in the United States for the past four decades, according to data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. Despite this progress, the outlook for patients diagnosed with the disease is not great; the overall five-year relative survival rate is just 66 percent. For those diagnosed with metastatic disease, things are even worse, just 17 percent are alive five years later.

The FDA also approved the PD-L1 IHC 22C3 pharmDx test as the companion diagnostic test to identify patients whose cervical cancers express PD-L1 and are eligible for treatment with pembrolizumab.

According to the FDA announcement, the approval was based on results from 77 patients with recurrent or metastatic, PD-L1 positive cervical cancer enrolled in the phase II KEYNOTE-158 clinical trial. Among these patients, two had complete tumor shrinkage and nine had partial tumor shrinkage, giving an overall response rate of 14.3 percent. After a median follow-up of 11.7 months, 91 percent of the 11 responses had lasted six months or longer.

Of note, there were several other cervical cancer patients enrolled in the trial whose recurrent or metastatic disease did not test positive for PD-L1. None of these patients had a response after receiving pembrolizumab.

The FDA approval of the therapeutic and the test was rendered on June 12, 2018. Find out more about the decision on the FDA website.