Pembrolizumab Plus Chemoradiotherapy Approved for Cervical Cancer
The FDA expanded the indications for pembrolizumab to include more patients with stage III-IVA cervical cancer.
The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda) plus chemoradiotherapy (CRT) for the treatment of patients with stage III-IVA cervical cancer as assessed by the FIGO 2014 staging criteria.
Pembrolizumab is an immunotherapy known as an immune checkpoint inhibitor. It interferes with one of the immune system’s natural “brake” systems that prevent immune cell overactivity. Many cancers exploit this brake system to hide from the immune system, but pembrolizumab blocks a protein called PD-1 to help the immune system stay active and destroy cancer cells.
Pembrolizumab is currently approved to treat patients with unresectable or metastatic cervical cancer whose tumors are characterized as microsatellite instability-high, mismatch repair deficient, or having a high tumor mutation burden—genetic features that increase the likelihood that immune checkpoint inhibitors will be effective. Pembrolizumab is also approved to treat recurrent or metastatic cervical cancer that expresses PD-L1, the activator of PD-1, after progression on or following chemotherapy. The latest approval enables all eligible patients with stage III-IVA cervical cancer to receive pembrolizumab plus CRT, including in the first-line setting, regardless of the presence of PD-L1, other tumor biomarkers, or receipt of prior therapy.
The approval was based on results from the multicenter, randomized, double-blind, placebo-controlled, phase III KEYNOTE-A18 clinical trial of patients with cervical cancer who had not previously received surgery, radiation, or systemic therapy. Of these patients, 596 had FIGO stage III-IVA disease, and 462 patients had FIGO stage IB2-IIB disease. Patients were randomly assigned (1:1) to receive CRT plus either pembrolizumab or a placebo.
In an exploratory analysis of patients with stage III-IVA disease, those in the pembrolizumab arm had a 41% lower chance of disease progression or death than those in the placebo arm. Conversely, among patients with stage IB2-IIB disease, those in the pembrolizumab arm had a 9% lower chance of disease progression or death than those in the placebo arm, a difference that was not considered clinically meaningful.
The recommended dosing regimen is 200 mg of pembrolizumab by intravenous (IV) administration every three weeks or 400 mg of pembrolizumab by IV every six weeks. Treatment may continue for up to 24 weeks or until disease progression or unacceptable toxicity. When given on the same day as CRT, pembrolizumab should be administered first.
Cervical cancer is relatively rare in the United States due to robust prevention and screening programs but is more common in other parts of the world, especially in low-resource settings. According to federal statistics, it was estimated that 13,960 individuals would be diagnosed with cervical cancer and 4,310 patients would die of the disease in the United States in 2023.
The FDA rendered its decision on January 12, 2024.
