On June 12, 2018, the U.S. Food and Drug Administration (FDA) approved the immunotherapy pembrolizumab (Keytruda®, Merck), which targets the PD-1 immune checkpoint, for patients with advanced, treatment-resistant cervical cancer that expresses PD-L1. Pembrolizumab blocks one of the immune system’s “braking mechanism” that some tumors exploit to avoid elimination by immune cells called T cells.
The FDA’s approval was based on results from the phase II KEYNOTE-158 trial. As part of that trial, 98 patients with advanced cervical cancer were treated with pembrolizumab. Among the 77 patients with PD-L1-positive tumors (combined proportion score, or CPS, greater than or equal to 1), 14.3% responded, and 91% of these responses lasted six months or more. On the contrary, none of the 21 patients with CPS less than 1 responded. Overall, the profile of immune-related adverse events was typical of PD-1 checkpoint inhibition—39% of patients experienced serious side effects, and 8% had to discontinue treatment.
“Keytruda is now the first anti-PD-1 therapy approved for the treatment of advanced cervical cancer, providing an important new second-line option for certain patients with this disease,” said Roy Baynes, M.D., Ph.D., Merck’s senior vice president and head of global clinical development and chief medical officer, in a company statement.
Following the VEGF-targeting antibody bevacizumab, which hampers a tumor’s ability to generate oxygen-supplying blood vessels, pembrolizumab is now the second immunotherapy approved for cervical cancer patients. This marks the seventh major cancer type in which subsets of patients can receive pembrolizumab, including lymphoma, melanoma, lung cancer, bladder cancer, head and neck cancer, and stomach cancer.
Additionally, pembrolizumab received a landmark approval to treat patients with any type of solid cancer, so long as it is metastatic (spread to other organs), resistant to treatment, and characterized by high microsatellite instability (MSI-hi).