ENGOT-cx11/GOG-3047/KEYNOTE-A18 study

Prof Domenica Lorusso, a gynaecological oncologist at Humanitas San Pio X, Milan, Italy, presented findings from the ENGOT-cx11/GOG-3047/KEYNOTE-A18 study during the presidential session. 

The study evaluated the novel use of pembrolizumab in combination with concurrent chemoradiation therapy (CCRT) in the treatment of locally advanced, high-risk cervical cancer. For over 25 years, CCRT has been the standard of care for this disease. Advances in radiotherapy, particularly image-guided techniques, have improved outcomes, with a five-year cure rate of 75% and local control in over 90% of cases. However, the study aimed to determine whether adding immunotherapy to CCRT could further enhance these outcomes, especially in high-risk patients. Preclinical and clinical evidence suggests that combining immunotherapy with CRT may improve efficacy. 

The trial enrolled 1,060 patients with high-risk cervical cancer as defined by FIGO 2014 staging (FIGO stages 1b, 2b, node-positive, and stages 3-4 regardless of lymph node status). Participants were randomised to receive standard CRT and brachytherapy either with pembrolizumab (200 mg every three weeks for five cycles, followed by 400 mg every six weeks for 15 cycles) or placebo, with a maintenance period of approximately two years. The trial had PFS and OS as primary endpoints. 

At three years, the trial met both endpoints, demonstrating a significant reduction in the risk of progression with a HR of 0.68. Notably, the median PFS was not reached in either arm, but the addition of pembrolizumab resulted in a 20% higher rate of PFS at three years. Additionally, there was a 33% reduction in the risk of death in the pembrolizumab arm, with 83% of patients alive at three years, compared to 75% in the standard treatment group.

The safety profile of pembrolizumab was manageable, with the most common adverse events being mild to moderate nausea, diarrhea, and anaemia. The toxicity profile was comparable between both treatment groups, and patient’s quality of life was not compromised. 

Based on these results, the combination of pembrolizumab with CCRT is proposed as the new standard of care for high-risk, locally advanced cervical cancer. This regimen should also be considered the appropriate control arm in future clinical trials.