Expanded Use of Immunotherapy Could Benefit Patients with Cervical Cancer

 Each year in the United States, about 14,480 women are diagnosed with cervical cancer, and about 4,290 women die of the disease. Survivors often face a lifetime of complications, from infertility to pain and bleeding.  

Vaccination against the human papillomavirus (HPV) is proving to be a powerful tool to prevent cervical cancer. More than 90 percent of cervical cancer cases arise from HPV infection, and vaccines are more than 90 percent effective in preventing cervical cancer and several other HPV-related cancers, such as anal, penile, vaginal, vulval, and oropharyngeal cancer. 

While nearly 92 percent of women whose cervical cancer is diagnosed at an early stage are expected to survive five or more years past their diagnosis, the five-year survival rate plunges to 58 percent for those whose disease has spread to the lymph nodes, and less than 18 percent for those whose disease has spread to other parts of the body.  

In a paper published in Clinical Cancer Research in September 2021, Louise Ferrall, research program coordinator in the Department of Pathology at Johns Hopkins University, explained that until very recently, most women diagnosed with cervical cancer were treated with chemotherapy. This strategy has been “woefully inadequate” for patients with advanced or metastatic disease, Ferrall wrote.  

In June 2018, the U.S. Food and Drug Administration issued the first approval of the immune checkpoint inhibitor pembrolizumab (Keytruda) for certain patients with metastatic or treatment-resistant cervical cancer. According to the Clinical Cancer Research paper, only about 15 percent of patients who received pembrolizumab in this context responded. 

In October 2021, the FDA opened the door to much wider use of pembrolizumab in cervical cancer treatment when it approved the drug as a first-line treatment for patients with cervical cancer whose tumors express high levels of PD-L1, as confirmed by an FDA-approved test. This approval allows pembrolizumab to be given in combination with chemotherapy, with or without bevacizumab.  

In the same action, the FDA approved pembrolizumab as a single agent for patients whose cervical cancer progressed after chemotherapy.  

The October approval was based on data from the KEYSTONE-826 clinical trial. The trial enrolled 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy. Patients were enrolled irrespective of PD-L1 expression status. 

Patients were randomly assigned to one of two treatment groups: One group received 200 mg of pembrolizumab plus chemotherapy, with or without bevacizumab; the other group received placebo plus chemotherapy, with or without bevacizumab.  

In all, 548 patients had tumors expressing PD-L1 with a combined positive score of 1 or greater. The median overall survival was not reached in the pembrolizumab arm and was 16.3 months in the placebo arm. Median progression-free survival was 10.4 months in the pembrolizumab arm and 8.2 months in the placebo arm. The overall response rate was 68 percent in the pembrolizumab arm, with a median duration of response of 18.0 months, compared with an overall response rate of 50 percent and duration of response of 10.4 months in the placebo arm. 

Shortly before the FDA issued its extended approval, clinical trial results were presented at the September ESMO Congress 2021. At the meeting, Antonio González-Martín, MD, director of the cancer center at the Clínica Universidad de Navarra in Madrid, Spain, described the trial results as a welcome outcome for cervical cancer patients, saying, “Patients with persistent, recurrent or metastatic cervical cancer have suffered historically from a dismal prognosis with an overall survival no longer than 12 months. The KEYNOTE-826 study is a new milestone, demonstrating a very relevant increment in the overall survival of patients with this condition and, for the first time, showing that incorporating immunotherapy into front-line treatment can change the natural history of the disease.” 

Because cervical cancer nearly always develops from persistent infection with the human papillomavirus, researchers see significant potential for immunotherapeutic approaches to this cancer type. Ongoing research is examining new immunotherapy strategies, such as live vector-based vaccines, dendritic cell-based vaccines, DNA- and RNA-based vaccines, and adoptive T-cell therapies. Studies are also examining combination therapies, with immunotherapeutics given along with chemotherapy or radiotherapy.  

“In all, immunotherapy is a promising approach for cervical cancer … We are hopeful for the future of cervical cancer immunotherapy given the breadth of novel treatments under development,” concluded Ferrall and corresponding author T.-C. Wu, MD, PhD, professor of pathology at the Johns Hopkins School of Medicine and director of gynecologic pathology at The Johns Hopkins Hospital.  

January is Cervical Cancer Awareness Month. To learn more about this disease, please see this January 2021 post on advances in prevention, screening, and treatment; and this September 2021 post on the history and current status of HPV vaccination.