Pembrolizumab Plus CCRT Scores in East Asian Subgroup With Cervical Cancer

In the East Asia subgroup of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945), pembrolizumab (Keytruda) plus concurrent chemoradiotherapy (CCRT) demonstrated a higher progression-free survival (PFS) rate vs placebo plus CCRT for patients with high-risk, locally advanced cervical cancer. Yang Xiang presented data during the European Society for Medical Oncology Gynaecological Cancers Congress 2024.¹

“China accounts for one-fifth [21.4%] of all new cases [and 19.4% of deaths] reported worldwide, and today we share the [East] Asian subgroup data,” Xiang, professor, doctoral tutor, and director of the Gynecological Oncology Center at Peking Union Medical College Hospital, executive president of the 18th Study on Trophoblastic Disease, and vice chairman of the Gynecologic Oncology Branch of the Chinese Medical Association in Beijing, China, said.

In the experimental arm, 152 patients received treatment with pembrolizumab plus CCRT, with 64.5% continuing treatment, 11.8% completing treatment, and 23.7% discontinuing treatment. In the control arm, 146 patients received treatment with placebo plus CCRT, with 55.5% continuing treatment, 10.3% completing treatment, and 34.2% discontinuing treatment.

At 24 months, the PFS rate in the experimental arm was 77.6% (range, 69.0%-84.0%), and in the control arm, the PFS rate was 59.8% (range, 48.5%-69.3%). The HR was 0.55 (95% CI, 0.35-0.88). These PFS rates showed a greater difference than PFS rates in the overall population, which were 67.8% (range, 61.8%-73.0%) in the experimental arm and 57.3% (range, 51.2%62.9%) in the control arm. The HR was 0.70 (95% CI, 0.55-0.89; P = .0020), and the median PFS was not reached across both arms in the overall population, including the East Asian subgroup.

Two patients withdrew with consent from the experimental arm. Four withdrew with consent and another through physician decision in the control arm.

Overall, 1060 patients were enrolled and randomly assigned 1:1 to the 2 treatment arms across 176 sites in 30 countries. Of these patients, 299 were enrolled in East Asian: 149 from China, 90 from Japan, 26 from South Korea, 20 from Thailand, and 14 from Taiwan.

There were 8 patients who had a PD-L1 combined positive score (CPS) of less than 1 in the experimental arm and 144 patients who had a PD-L1 CPS of 1 or greater. In the control arm, there were 10 patients with a PD-L1 CPS of less than 1 and 134 patients with a PD-L1 CPS of 1 or greater. Of those with an ECOG performance score of 1, there were 59 patients in the experimental arm and 38 in the control arm, and there were 141 and 131 patients, respectively, with squamous cell carcinoma.

In the experimental arm, patients received 40 mg/m² of cisplatin weekly for 5 cycles, plus external beam radiotherapy (EBRT) followed by brachytherapy, plus pembrolizumab at a dose of 200 mg every 3 weeks for 5 cycles. This was followed by an additional 15 cycles of 400 mg of pembrolizumab every 6 weeks. In the control arm, patients received 40 mg/m2 of cisplatin weekly for 5 cycles plus EBRT followed by brachytherapy, plus placebo every 3 weeks for 5 cycles and the additional 15 cycles of placebo every 6 weeks.

“The treatment exposure was well matched between the 2 groups with a similar median [number] of cycles for pembrolizumab or placebo,” Xiang said. Patients in the experimental arm completed a median of 14 cycles of pembrolizumab; for those in the control arm, there was a median of 13 cycles with placebo. Both groups received a median of 5 cycles of cisplatin. The overall treatment time, crucial for therapeutic efficacy, averaged 52 days for the experimental arm and 51 days for the control arm. In the experimental arm, 72.4% of patients completed radiation therapy within 56 days vs 79.9% in the control arm.

Those eligible 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 RECIST v1.1 measurable or nonmeasurable disease and were treatment naive. The primary end points were PFS, confirmed through RECIST v1.1 by investigator or histopathologic examination, and overall survival. Secondary end points included 24-month PFS, overall response rate, patient reported outcomes, and safety. Patients were stratified by planned EBRT type, stage at screening, and planned total radiotherapy.

The safety profile for the experimental arm in patients from East Asia was manageable and consistent with the overall population. In both arms, all patients from the East Asian subgroup experienced any-grade, allcause 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 were observed in 78.3% vs 77.4% of patients, and serious TRAEs were observed in 22.4% vs 9.6% of patients, respectively.

Immune-mediated AEs were observed in 43.3% of patients in the experimental arm and 10.3% in the control arm. Grade 3 or greater immune-mediated AEs were observed in 3.3% vs 0.7%, and serious immune-mediated AEs were observed in 2.6% vs 0.7%, respectively. All-cause AEs leading to treatment discontinuation were reported in 19.1% of patients in the experimental arm and 23.3% in the control arm; TRAEs resulting in treatment discontinuation were reported in 18.4% vs 21.9%, respectively. 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%), Xiang said.

Regarding the overall population of the trial, nearly all patients in both treatment groups experienced AEs, with slightly higher rates observed among those receiving pembrolizumab. Specifically, 99.4% of patients in the experimental arm and 99.2% in the control arm reported any-grade AEs.

“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,” Xiang said.

REFERENCE:

Xiang Y, Hasegawa K, Zhu H, et al. A randomized, phase III, double-blind study of chemoradiotherapy with or without pembrolizumab in patients with high-risk, locally advanced, cervical cancer (KEYNOTE-A18/ENGOT-cx11/GOG-3047): results for patients enrolled in Asia. ESMO Open. 2024;9(suppl 5):103523. doi:10.1016/j.esmoop.2024.103253