▎WuXi AppTec Content Team Report

On December 10, MSD announced that its PD-1 inhibitor pembrolizumab had been approved by the National Medical Products Administration (NMPA) of China.Concurrent chemoradiotherapy for the treatment of International Federation of Gynecology and Obstetrics (FIGO) 2014 stage III-IVA cervical cancer patientsAccording to the MSD press release, this is the first cervical cancer indication approved for pembrolizumab in China.

Epidemiological data show that approximately 37% of cervical cancer patients are diagnosed at a locally advanced stage. Although the level of diagnosis and treatment for cervical cancer in China has significantly improved in recent years, the 5-year overall survival rate remains low, at only 50%-60%, due to factors such as large local tumor volume, often accompanied by high-risk conditions like lymph node metastasis and parametrial invasion, which make distant metastasis more likely to occur after treatment.

According to the MSD press release, the approval of this new indication was based on the data from the global Phase 3 clinical trial KEYNOTE-A18.In April 2024, The Lancet published the results of the KEYNOTE-A18 trial, indicatingIn patients with locally advanced cervical cancer, adding pembrolizumab to chemoradiotherapy significantly improved progression-free survival, reducing the risk of disease progression and death by 30%.. The editorial in the same period pointed out,This research advances the role of immunotherapy in cervical cancer, transforming clinical practice.

Screenshot source:The Lancet

This was a randomized, double-blind, placebo-controlled Phase 3 clinical trial (code name ENGOT-cx11/GOG-3047/KEYNOTE-A18), conducted across 176 medical centers in 30 countries worldwide from 2020 to 2022. A total of 1,060 newly diagnosed high-risk patients with locally advanced cervical cancer were randomly assigned to receive either pembrolizumab combined with chemoradiotherapy (529 patients) or placebo combined with chemoradiotherapy (531 patients).

As of January 2023, the median follow-up time for patients in both groups was 17.9 months.There was a significant statistical difference in progression-free survival between the two groups, with a higher 2-year progression-free survival rate in the pembrolizumab combined with chemoradiotherapy group.（68% vs 57%），The risk of disease progression or death was significantly reduced by 30%.Moreover, consistent trends were observed across different subgroup analyses.

The 2-year overall survival rate was also higher in the pembrolizumab plus chemoradiotherapy group.(87% vs 81%), the difference in mortality risk has not yet reached statistical significance, but shows a trend of 27% reduction.Early overall survival data support progression-free survival results.

References:

[1] MSD's PD-1 Inhibitor Keytruda® Approved in China for Locally Advanced Cervical Cancer Treatment Indication.. Retrieved Dec 10，2024, From  https://mp.weixin.qq.com/s/rHiUhOdMnt4BfOdFqGPVCA

[2] Domenica Lorusso, et al., (2024). Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. The Lancet, DOI: https://doi.org/10.1016/S0140-6736(24)00317-9