Pembrolizumab plus platinum-based chemotherapy with or without bevacizumab significantly improved overall survival and progression-free survival over the same platinum-based chemotherapy regimen with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer—irrespective of PD-L1 status.
Pembrolizumab (Keytruda) plus platinum-based chemotherapy with or without bevacizumab (Avastin) significantly improved overall survival (OS) and progression-free survival (PFS) over the same platinum-based chemotherapy regimen with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer—irrespective of PD-L1 status, meeting the primary end point of the phase 3 KEYNOTE-826 trial (NCT03635567).1
Pembrolizumab is the first anti–PD-1/PD-L1 agent to showcase this benefit in this population, according to Merck.
Additional data from the interim analysis showed that the toxicity profile of the immunotherapy in this trial proved to be consistent with what has been observed in prior research.
Merck announced plans to submit these data to regulatory authorities. The findings will also be presented at an upcoming medical conference.
“Women diagnosed with metastatic cervical cancer have a particularly poor prognosis, and there is an urgent need for new treatment options,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, stated in a press release. “KEYNOTE-826 is the first study to show positive results for immunotherapy in first-line persistent, recurrent or metastatic cervical cancer, and we look forward to sharing these findings at an upcoming congress and discussing them with regulatory authorities.”
In June 2018, the FDA granted an accelerated approval to pembrolizumab for the second-line treatment of patients with recurrent or metastatic cervical cancer who experienced disease progression on, or after, chemotherapy, and whose tumors express PD-L1.2 The decision was based on data collected from 98 patients with recurrent or metastatic cervical cancer who were enrolled to a single cohort in the phase 2 KEYNOTE-158 trial (NCT02628067).
At a median follow-up of 11.7 months, the immunotherapy elicited an overall response rate (ORR) of 14.3% (95% CI, 7.4-24.1) in 77 patients with PD-L1 positivity who had received prior treatment with at least 1 line of chemotherapy in the metastatic setting. The median duration of response (DOR) had not yet been reached. Ninety-one percent of responders experienced a response that persisted for 6 months or longer.3
The continued approval for the indication is contingent upon verification and description of clinical benefit in confirmatory trials. The triple-blind, phase 3 KEYNOTE-826 is the confirmatory trial for this approval.
For the trial, investigators set out to examine the safety and efficacy of pembrolizumab plus platinum-based chemotherapy in the form of paclitaxel plus cisplatin or paclitaxel plus carboplatin, with or without bevacizumab vs placebo plus the same platinum-based chemotherapy combinations with or without bevacizumab in the frontline treatment of adult patients with persistent, recurrent, or metastatic cervical cancer.
To be eligible for enrollment, patients needed to have persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix who were no longer candidates for curative treatment such as surgery and/or radiation. Patients also needed to have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and acceptable organ function.4 They could not have received prior treatment with systemic chemotherapy.
The primary end points of the study are OS and PFS, and key secondary end points include ORR, DOR, and safety.
A total of 617 patients were enrolled to the trial. Patients on the investigative arm received intravenous (IV) pembrolizumab at a dose of 200 mg in combination with investigator’s choice of a platinum-based chemotherapy regimen: paclitaxel at 175 mg/m2 plus cisplatin at 50 mg/m2 with or without bevacizumab at 15 mg/kg; paclitaxel at 175 mg/m2 plus carboplatin at area under the curve (AUC) 5 with or without bevacizumab at 15 mg/kg on day 1 of each 21-day treatment cycle for up to 35 cycles. Those in the control arm received just 1 of the 2 platinum-based chemotherapy regimens alone at the same dosing and schedule.