The recent approvalof Keytruda (pembrolizumab) by the Food and Drug Administration (FDA) plus chemoradiotherapy (CRT) for the treatment of patients with stages 3 to 4A cervical cancer marked the first approval of an anti-PD-1 therapy in combination with chemotherapy for this patient population, as well as the third FDA approval for the treatment of cervical cancer with Keytruda.
“I’m in central Virginia, and in rural areas like this, we have so much cervical cancer, and it’s horrible because this is a completely preventable disease,” said Dr. Linda R. Duska, a gynecologic oncologist at the University of Virginia Health and the United States principal investigator on KEYNOTE-A18, the study which served as the basis of the recent FDA approval.
“My opinion is in the U.S., women shouldn’t have this disease at all, because we have a robust, really successful screening program and we have a safe, effective vaccine,” Duska said. “We shouldn’t be seeing this disease in the U.S. at all, yet, somehow we see close to 11,000 patients a year. And in particular, in central Virginia, we see a lot of this disease.
“So, this is our chance, upfront, to cure these women. This is the best chance we have to cure them. And so, if we have an opportunity in these advanced-stage patients to give them a better chance of cure, then that’s a really huge thing for our patients.”
The KEYNOTE-A18 trial enrolled 1,060 patients with cervical cancer who had not been previously treated with surgery, radiation or systemic therapy, including 596 patients with stage 3 to 4A disease and 462 patients with stage 1B2 to 2B, node-positive disease, according to the FDA.
“There was an improvement in progression-free survival (PFS; the time a patient lives without their disease spreading or worsening) for the groups that got the (Keytruda), there was a 30% decrease in progression for those individuals that got the combination (of Keytruda and chemotherapy),” Duska noted. “And it wasn’t a lot more toxic — there were some toxicities that go along with (Keytruda) that we’re seeing in the (Keytruda) arm, but it wasn’t particularly more toxic than chemo (and) radiation by itself. So, that was really remarkable.”
Data from KEYNOTE-A18 presented at the 2023 ESMO Congress showed that 24-month rates of progression-free survival were 67.8% and 57.3% among patients treated with Keytruda and those who received placebo, while those cohorts’ 24-month rates of overall survival (OS; the time a patient lives following treatment regardless of disease status) were 87.2% and 80.8%. Overall response rates (ORR; patients whose disease partially or completely responded to treatment were 79.3% and 75.9%, with complete response rates of 50.7% and 48.7%.
Treatment with Keytruda resulted in a 41% reduction in the risk of disease progression or death when compared with placebo in the phase 3 trial, according to a news release from Merck, the manufacturer of Keytruda.
Additionally, Duska noted, that overall survival is not yet available for KEYNOTE-A18, meaning more than half of the patients enrolled in the study are still alive.
“The overall survival data is not mature — in fact, more than half of patients are still being treated on study right now.”
Dr. Bradley Monk, oncologist and professor of obstetrics and gynecology at the University of Arizona’s College of Medicine and Creighton University School of Medicine, called the approval welcome news in a statement issued in Merck’s news release.
“This Keytruda-based regimen offers a new treatment option for these patients, so today’s approval has important implications for the way we treat them moving forward,” Monk said.
Side effects experienced by at least 10% of patients participating in KEYNOTE-A18 and treated with Keytruda and CRT included nausea, diarrhea, vomiting, urinary tract infection, fatigue, hypothyroidism, constipation, decreased appetite, weight loss, abdominal pain, pyrexia (fever), hyperthyroidism, dysuria (painful urination), rash and pelvic pain, according to the FDA.
Per the FDA, the recommended dosing regimen for Keytruda is 200 mg administered intravenously every three weeks, or 400 mg every six weeks, until disease progression, unacceptable toxicity or up to 24 months. When Keytruda and CRT are given on the same day, the agency advised that Keytruda should be given first.
As Duska noted, while the FDA approved the regimen for patients with advanced disease KEYNOTE-A18 also enrolled patients with stages 1B2 to 2B cervical cancer with node-positive disease.
“The FDA didn’t (approve) the entire group that was entered into the trial, the FDA only (approved) for those patients with stage 3 and 4 disease,” Duska said. “Now, that might change as we get more data. And I would expect that to change as we get more data.”
For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.