Patients with persistent, recurrent or metastatic cervical cancer treated with Keytruda plus chemotherapy with or without Avastin (bevacizumab) had substantially improved survival compared with placebo plus chemotherapy with or without Avastin, findings from a study analysis demonstrated.
Findings from this final overall survival (the time from treatment that a patient with cancer is still alive) analysis of the phase 3 KEYNOTE-826 trial were presented at a 2023 ASCO Annual Meeting pre-meeting press briefing.
At a median follow-up of 39.1 months, patients assigned Keytruda (308 patients) had a median overall survival of 26.4 months compared with 16.8 months for those in the placebo group (309 patients). The 12- and 24-month overall survival rates in the Keytruda group were 74.9% and 52.1%, respectively. In the placebo group, those rates were 63.7% and 38.7%, respectively.
Notably, 88.8% of enrolled patients had a PD-L1 combined positive score of at least 1, indicating the number of PD-L1 positive cells in relation to tumor cells. Among this subgroup, Keytruda plus chemotherapy with or without Avastin elicited a median overall survival of 28.6 months versus 16.5 months for placebo plus chemotherapy with or without Avastin.
The 12- and 24-month overall survival rates for patients with a PD-L1 combined positive score of at least 1 in the Keytruda arm were 75.5% and 53.5%, respectively. Those rates were 63.2% and 39.4%, respectively, in patients with a PD-L1 combined positive score of at least 1 treated with the placebo regimen.
“Before KEYNOTE-826, the standard of care was a platinum-based paclitaxel chemotherapy combination with or without (Avastin) treatment for people with this diagnosis,” lead study author Dr. Bradley J. Monk, professor in the division of gynecologic oncology at Creighton University School of Medicine in Phoenix, stated in a news release. “This study demonstrates that giving immunotherapy earlier provides a substantial (overall survival) benefit compared with the second-line setting. Our results also show a survival benefit of (Keytruda) in patients who are not eligible for (Avastin), offering a therapeutic option in this population of patients with a high unmet need.”
In October 2021, the FDA approved Keytruda for use in combination with chemotherapy, with or without Avastin, in patients with persistent, recurrent, or metastatic cervical cancer whose tumors have a PD-L1 combined positive score of 1 or higher, as determined by an FDA-approved test, based on prior data from KEYNOTE-826.
Researchers conducting the trial enrolled patients with persistent, recurrent or metastatic cervical cancer that was not amenable to curative treatment. No prior systemic chemotherapy was permitted, although previous radiotherapy or chemoradiotherapy was allowed.
Patients were randomly assigned to receive Keytruda or matching placebo in combination with chemotherapy with or without Avastin.
The main focus of this trial was to assess overall survival and progression-free survival, which is the time during and after treatment when a patient with cancer is alive without the disease worsening. Other areas of interest included overall response rate (the percentage of patients with a partial or complete response to treatment), duration of response (the time from treatment to disease progression or death in patients with a complete or partial response to treatment), 12-month progression-free survival rate and safety.
Additional data showed that the Keytruda regimen also produced an overall survival benefit versus the placebo regimen in patients with a PD-L1 combined positive score of at least 10. In this subgroup, the Keytruda regimen generated a median overall survival of 29.6 months compared with 17.4 months for the placebo regimen.
The final analysis also demonstrated that Keytruda plus chemotherapy with or without Avastin elicited a progression-free survival benefit in all patients in the trial (10.4 months versus 8.2 months), the PD-L1 combined positive score of at least 1 subgroup and PD-L1 combined positive score of at least 10 subgroup. Survival benefits were observed in the subgroups of patients who did and did not receive Avastin.
The Keytruda regimen also led to a higher overall response rate and longer duration of response compared with the placebo regimen.
Regarding safety, Keytruda plus chemotherapy with or without Avastin was manageable, and side effects were consistent with the known profiles of the individual agents. Long-term follow-up did not reveal any new safety signals.
In the Keytruda group, 82.4% of patients experienced severe or worse side effects compared with 75.4% of patients in the placebo group. The most common severe or worse side effects in the Keytruda group versus the placebo arm included anemia (30.3% versus 27.8%), neutropenia (12.4% versus 9.7%) and high blood pressure (10.4% versus 11.7%).
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