Pembrolizumab plus concurrent chemoradiotherapy (CCRT) has demonstrated a significant improvement in progression-free survival (PFS) for East Asian patients with high-risk, locally advanced cervical cancer. The findings, presented at the European Society for Medical Oncology Gynaecological Cancers Congress 2024, highlight the potential of this combination as a new treatment option for a region with a substantial burden of cervical cancer.
The phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945) evaluated the efficacy and safety of pembrolizumab (Keytruda) plus CCRT versus placebo plus CCRT in patients with high-risk, locally advanced cervical cancer. The East Asian subgroup analysis revealed a notable difference in PFS rates at 24 months, with 77.6% (range, 69.0%-84.0%) in the pembrolizumab arm compared to 59.8% (range, 48.5%-69.3%) in the placebo arm (HR, 0.55; 95% CI, 0.35-0.88).
Study Details and Patient Population
The study enrolled 1060 patients across 176 sites in 30 countries, with 299 patients from East Asia (149 from China, 90 from Japan, 26 from South Korea, 20 from Thailand, and 14 from Taiwan). Eligible patients had International Federation of Gynecology and Obstetrics 2014 stage IB2 to IIB (node-positive disease) or stage III to IVA (node-positive or node-negative disease) and were treatment-naive.
Patients in the experimental arm received pembrolizumab (200 mg every 3 weeks for 5 cycles, followed by 400 mg every 6 weeks for 15 cycles) plus CCRT, consisting of cisplatin (40 mg/m2 weekly for 5 cycles) and external beam radiotherapy (EBRT) followed by brachytherapy. The control arm received placebo plus the same CCRT regimen.
The primary endpoints were PFS, confirmed by RECIST v1.1, and overall survival. Secondary endpoints included 24-month PFS, overall response rate, patient-reported outcomes, and safety.
Safety Profile
The safety profile of pembrolizumab plus CCRT in the East Asian subgroup was manageable and consistent with the overall population. All patients in both arms experienced any-grade, all-cause adverse events (AEs). Treatment-related AEs (TRAEs) were observed in 98.7% of patients in the experimental arm and 98.6% in the control arm. Grade 3 or greater TRAEs occurred in 78.3% versus 77.4% of patients, and serious TRAEs in 22.4% versus 9.6%, respectively.
Immune-mediated AEs were more frequent in the pembrolizumab arm (43.3%) compared to the placebo arm (10.3%). The most common grade 1 or 4 TRAEs in the East Asian subgroup were related to blood: anemia (70.4% vs 69.9%), decreased white blood cells (69.1% vs 67.8%), and decreased neutrophils (65.8% vs 61.6%).
Clinical Significance
"These results suggest that pembrolizumab plus CCRT may be considered as a new treatment option for patients with high-risk locally advanced cervical cancer in East Asia," said Yang Xiang, professor, doctoral tutor, and director of the Gynecological Oncology Center at Peking Union Medical College Hospital. Given that China accounts for a significant proportion of new cervical cancer cases and deaths worldwide, this finding is particularly relevant for improving treatment outcomes in the region.
