Pembrolizumab + CCRT ups survival in high-risk LACC

Treatment with the combination of pembrolizumab and concurrent chemoradiotherapy (CCRT), followed by pembrolizumab maintenance, led to a sustained, long-term survival benefit in patients with high-risk, locally advanced cervical cancer (LACC) compared with CCRT alone, according to the final analysis of the phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial presented at ASCO 2025.

With a median follow-up of 41.9 months, patients treated with pembrolizumab + CCRT demonstrated a sustained improvement in progression-free survival (PFS), showing a 28-percent reduction in the risk of disease progression (hazard ratio [HR], 0.72) compared with those treated with CCRT alone.

In addition, the combination arm demonstrated higher PFS rates at 24 and 36 months (70.6 percent vs 59.7 percent and 64.3 percent vs 55.6 percent, respectively) than the CCRT only arm.

Overall survival (OS) rates were also higher among patients treated with pembrolizumab + CCRT compared with CCRT alone (81.8 percent vs 74.4 percent at 36 months and 75.4 percent vs 70.2 percent at 48 months).

The OS benefit favouring pembrolizumab + CCRT over CCRT alone was consistently observed across all protocol-specified subgroups, except for patients aged ≥65 years (HR, 1.18).

“After an additional 12 months of median follow-up, pembrolizumab combined with modern, high-quality CCRT and then continued after CCRT continued to show clinically meaningful improvements in OS and PFS vs CCRT alone in participants with newly diagnosed, previously untreated, high-risk LACC,” said lead author Dr Linda Duska from the University of Virginia School of Medicine in Charlottesville, Virginia, US. [ASCO 2025, abstract LBA5504]

The ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial included 1,060 patients with high-risk LACC (defined as FIGO 2014 stage IB2–IIB [node-positive disease] or stage III–IV [either node-positive or -negative disease]).

Participants were randomly assigned to receive pembrolizumab 200 mg Q3W for five cycles (pembrolizumab + CCRT arm, n=529) or placebo (CCRT alone arm, n=531) in addition to CCRT (cisplatin 40 mg/m² QW for five cycles + EBRT* followed by brachytherapy), followed by maintenance treatment with pembrolizumab 400 mg Q6W for 15 cycles or placebo, respectively.

More than half of the participants completed the treatment, with 55.5 percent reported in the pembrolizumab + CCRT arm and 53.2 percent in the CCRT alone arm.

In terms of safety, treatment-related adverse events (TRAEs) of any grade were similar between the pembrolizumab + CCRT and CCRT alone arms (97 percent vs 96.8 percent). Grade ≥3 and serious TRAEs rates were 69.5 percent vs 61.5 percent and 19.7 percent vs 13.6 percent, respectively. Anaemia, nausea, and diarrhoea were the most common TRAEs in both arms.

However, two treatment-related deaths occurred in each arm.

Immune-mediated AEs of any grade occurred in 39.8 percent of patients in the pembrolizumab arm, whereas only 17.5 percent were observed in the CCRT alone arm. The most common immune-related AEs were hypothyroidism (22.9 percent vs 7.4 percent) and hyperthyroidism (12.1 percent vs 2.8 percent), but mostly were grade 1/2.

“The safety profile of pembrolizumab + CCRT was manageable and consistent with the known profiles of the individual therapies, with no new safety signals after longer follow-up,” said Duska.