Cervical cancer: PFS advantage with pembrolizumab plus CCRT consistent in Asians

Patients with high-risk locally advanced cervical cancer in East Asia get progression-free survival (PFS) boost with pembrolizumab plus concurrent chemoradiotherapy (CCRT), similar to those observed in the overall population of the phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study.

Results of an exploratory analysis presented at ESMO Gyn showed that the median PFS was not reached at the study cutoff in the pembrolizumab plus CCRT arm as well as in the placebo plus CCRT arm in the East Asia subgroup. The median follow-up was 19.3 months. [ESMO Gyn 2024, abstract 23O]

The 24-month PFS rates were 77.6 percent in the pembrolizumab group and 59.8 percent in the placebo group, with pembrolizumab plus CCRT being associated with a 45-percent reduction in the risk of disease progression or death (hazard ratio [HR], 0.55, 95 percent confidence interval [CI], 0.35–0.88), reported lead author Dr Yang Xiang from Peking Union Medical College Hospital, National Clinical Research Center for Obstetric & Gynecologic Diseases in Beijing, China.

Meanwhile, in the overall population, the 24-month PFS rates were slightly lower at 67.8 percent with pembrolizumab plus CCRT and 57.3 percent with placebo plus CCRT. The risk of disease progression or death was 30-percent lower in the pembrolizumab arm (HR, 0.70, 95 percent CI, 0.55–0.89).

These data indicate that the benefit of pembrolizumab plus CCRT is even more pronounced in the East Asia subgroup, Xiang said.

In terms of safety, the treatment was generally well tolerated in this subgroup, with manageable side effects, he added.

The frequency of grade ≥3 adverse events (AEs) were similar between the pembrolizumab and placebo arms (all-cause: 81.6 percent vs 80.1 percent; treatment-related: 78.3 percent vs 77.4 percent). However, more patients in the pembrolizumab arm had serious AEs (all-cause: 30.3 percent vs 19.9 percent; treatment-related: 22.4 percent vs 9.6 percent) and any-grade immune-mediated AEs (32.6 percent vs 11.7 percent). There was no significant difference in the rate of AEs leading to treatment discontinuation between the treatment arms. None of the patients died due to treatment-related AEs.

The most common treatment-related AEs in both the pembrolizumab and placebo arms were related to blood such as anaemia and low white blood cell and neutrophil counts. Nausea rates were also high. Xiang pointed out that diarrhoea, which is common with pembrolizumab and CCRT, was not more frequent in the pembrolizumab arm.

Looking at the overall population, the frequency of grade ≥3 AEs was likewise similar between the pembrolizumab and placebo arms (all-cause: 74.6 percent vs 68.7 percent; treatment-related: 67.0 percent vs 60.6 percent), as was that of serious AEs (all-cause: 28.4 percent vs 24.7 percent; treatment-related: 17.2 percent vs 12.3 percent). Two patients in each arm died due to treatment-related AEs (gastritis and large intestine perforation in the pembrolizumab arm, and bone marrow failure and neutropenic colitis in the placebo arm). Like in the East Asia subgroup, the most common treatment-related AEs were anaemia, nausea, and diarrhoea.

According to Xiang, the safety profile of pembrolizumab in the East Asia subgroup was quite similar to that in the overall population, indicating that the combination did not significantly increase the risk of AEs compared with standard treatment

Collectively, the findings “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,” he said.

The analysis included 299 patients who were enrolled in China, Japan, South Korea, Thailand, and Taiwan. Of these, 153 patients (median age 54 years) received pembrolizumab plus CCRT and 146 (median age 55 years) received placebo plus CCRT.  The combination arm received a median of 14 cycles of pembrolizumab. Median overall radiation treatment time was 52 days in the combination group (median cervix physical dose 74.8 Gy, median cervix EQD2 dose 85.5 Gy) and 51 days in the placebo group (median cervix physical dose 73.8 Gy, median cervix EQD2 dose 84.3 Gy).