Pembrolizumab Combo Improves OS in Metastatic Cervical Cancer Subgroups

“In this randomized clinical trial, the addition of pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer,” according to the study authors.

Adding pembrolizumab (Keytruda) to chemotherapy with or without bevacizumab (Avastin) elicited an overall survival (OS) improvement across multiple subgroups of patients with persistent, recurrent, or metastatic cervical cancer, according to updated findings from the phase 3 KEYNOTE-826 trial (NCT03635567).

Among patients with a PD-L1 combined positive score of at least 1 who received bevacizumab, the median OS was not reached (NR; 95% CI, 24.4-NR) in the pembrolizumab arm compared with 25.0 months (95% CI, 16.3-NR) in the placebo arm (HR, 0.62; 95% CI, 0.45-0.87). The median OS in each respective arm was 17.1 months (95% CI, 14.9-20.0) vs 11.9 months (95% CI, 9.7-14.5) among those who did not receive bevacizumab (HR, 0.67; 95% CI, 0.47-0.96). The HRs for progression-free survival (PFS) were 0.61 (95% CI, 0.46-0.80) in patients treated with bevacizumab and 0.66 (95% CI, 0.47-0.92) in those who did not receive bevacizumab.

In the pembrolizumab and placebo arms, respectively, the median OS was 24.4 months (95% CI, 18.7-NR) vs 15.7 months (95% CI, 13.2-18.6) in those who received carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and NR (95% CI, 22.3-NR) vs 24.7 months (95% CI, 16.0-NR) among patients treated with cisplatin (HR, 0.53; 95% CI, 0.27-1.04). The PFS HRs were 0.68 (95% CI, 0.53-0.85) and 0.39 (95% CI, 0.22-0.68) in the carboplatin subgroup and cisplatin subgroups, respectively.

Among patients who received prior chemoradiotherapy (CRT) only, the median OS was NR (95% CI, 17.0-NR) in the pembrolizumab arm compared with 11.9 months (95% CI, 9.3-14.8) in the placebo arm (HR, 0.56; 95% CI, 0.39-0.81). The median OS in each respective arm was NR (95% CI, 19.2-NR) vs 23.5 months (95% CI, 16.0-26.0) among those who did not receive prior CRT (HR, 0.72; 95% CI, 0.52-1.00). The estimated PFS HRs were 0.55 (95% CI, 0.39-0.78) in the prior CRT subgroup and 0.68 (95% CI, 0.52-0.90) among those who did not receive CRT.

The median OS with pembrolizumab and placebo, respectively, was 24.4 months (95% CI, 19.1-NR) vs 14.2 months (95% CI, 12.1-18.4) among patients with squamous histology (HR, 0.60; 95% CI, 0.46-0.79) and NR (95% CI, 17.3-NR) vs 23.5 months (95% CI, 16.3-NR) in those with nonsquamous histology (HR, 0.70; 95% CI, 0.41-1.20). Additionally, the HRs for PFS were 0.61 (95% CI, 0.48-0.78) in the squamous disease subgroup and 0.59 (95% CI, 0.37-0.93) among those with nonsquamous histology.

“In this randomized clinical trial, the addition of pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer,” the study authors wrote. “Additional studies of pembrolizumab combined with anti-TIGIT or anti–CTLA-4 checkpoint inhibitors, bispecific antibody engagers, and cellular-based immunotherapies including tumor-infiltrating lymphocytes and chimeric T-cell receptor antigens, are ongoing.”

In the KEYNOTE-826 trial, patients were randomly assigned to receive pembrolizumab at 200 mg (n = 308) or matched placebo (n = 309) plus chemotherapy with or without bevacizumab at 15 mg/kg.

The study’s primary end points were OS and PFS based on investigator assessment using RECIST v1.1 criteria. Objective response rate (ORR) based on RECIST v1.1 guidelines was a secondary end point.

Patients 18 years and older who had received no prior treatment for persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix not amenable to curative therapy were eligible to enroll on the trial. Those with prior receipt of radiotherapy or CRT at least 2 weeks before randomization were able to enroll.

Of 617 patients, the median age was 51 years (range, 22-82). Additionally, most patients had PD-L1–positive disease (89.0%). Most patients in the pembrolizumab group (63.6%) and placebo arm (62.5%) received bevacizumab. Baseline characteristics were generally comparable in the pembrolizumab and placebo arms.

Among patients with a CPS of at least 1, ORRs in the pembrolizumab arm ranged from 52.0% to 84.6% compared with 33.7% to 60.3% in the placebo arm. ORRs in the intent-to-treat population were anywhere between 49.1% and 82.0% in the pembrolizumab arm vs 34.5% and 62.2% in the placebo arm.

Reference

Tewari KS, Colombo N, Monk BJ, et al. Pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer subgroup analyses from the KEYNOTE-826 randomized clinical trial. JAMA Oncol. Published online December 14, 2023. doi:10.1001/jamaoncol.2023.5410