Immunotherapy has brought promising breakthroughs for several forms of cancer. Now, researchers are applying the knowledge they’ve gained in previous clinical trials as they look into how immunotherapy might provide additional treatment options for patients with recurrent cervical cancer.
The introduction of a vaccination and screening test for cervical cancer was a significant breakthrough in prevention and identification, but cervical cancer remains the second leading cause of cancer-related mortality in women.
“Cervical cancer is a huge worldwide problem that does not get enough attention,” says Ursula Matulonis, MD, director of Gynecologic Oncology at Dana-Farber’s Susan F. Smith Center for Women’s Cancers. “Throughout the world, 100,000 cases are diagnosed each year. Many of those cases are in Africa, South America and parts of Asia. It is a smaller problem in the United States, but still a problem: 13,000 cases diagnosed per year is not a trivial number.”
Approximately 4,200 women in the U.S. die each year from cervical cancer. A major challenge is the lack of approved regimens to treat the cancer when it recurs in some patients. “You have a population of women who have had recurrence after standard chemotherapy with bevacizumab (Avastin) and who have no other options,” Matulonis says. “There is a void there — a huge unmet need for treatment.”
Immunotherapy aims to fill that void, through therapies that harness a patient’s own immune system to attack the cancer. “Cervical cancer has a relatively high number of mutations (changes in the genes), which may make it more sensitive to immunotherapy drugs,” Matulonis says. “We have learned about immunotherapy approaches from other cancers and can potentially apply those results to cervical cancer.”
Early trials focused on single agents known as an anti-PD1 monoclonal antibodies. These remove a blockade created by the cancer cells that prevent or reduce the immune response. As a result, these “checkpoint inhibitors” allow the immune system to once again recognize the tumor and respond to it.
Researchers recently concluded a phase 2 trial of the single agent drug nivolumab (Opdivo) for recurrent cervical cancer. Of 24 patients — 19 with cervical cancer, 5 with vaginal cancer — 26 percent of patients with cervical cancer had a response to the drug. “That is encouraging activity,” says Matulonis.
Researchers will continue to refine the single-agent regimen through further trials, in the hope of identifying what makes one patient’s response more robust than another. But researchers are also pursuing an alternate path: Combination trials.
“Studies of single-agent immunotherapy with drugs like pembrolizumab (Keytruda) or nivolumab have shown activity in 15 percent to 25 percent of patients but without activity in the remaining patients,” says Panagiotis Konstantinopoulos, MD, director of Translational Research in the Gynecologic Oncology Program at Dana-Farber. “There is clearly a lot of room for improvement. For this reason, there are lots of efforts focusing on combination trials against cervical cancer.”
Konstantinopoulos is conducting a trial that pairs the immunotherapy drug atezolizumab (Tecentriq) with an antiangiogenic agent called bevacizumab, which blocks cancer cells from forming the new blood vessels they need to grow. “Bevacizumab is an active drug against cervical cancer, and there are also preclinical data that bevacizumab can improve the efficacy of immunotherapy,” he says. “Therefore, this is an exciting combination for cervical cancer and we are eagerly awaiting the results of this study.”
In another clinical trial, researchers are looking at how two immunotherapy drugs — durvalumab (IMFINZI) and tremelimumab — combine with radiotherapy, to see if radiation boosts the immune response.
Through its participation in the Experimental Therapeutics Clinical Trials Network (ETCTN), sponsored by the National Cancer Institute, Dana-Farber collaborates with other leading institutions in developing the next cutting-edge immunotherapy combination strategies. “Patients need to understand that the fact that clinical trials now exist for cervical cancer is hopeful,” Matulonis says. “It is hopeful. Two years ago, we had none.”