Background
Chemoradiation is a treatment for cervical cancer that combines two methods: radiotherapy and chemotherapy. Radiotherapy uses high-energy X-rays to kill cancer cells, and this can be done both externally (from outside the body) and internally (called brachytherapy). Chemotherapy, on the other hand, uses drugs, usually given into the vein, to target and destroy cancer cells. In this situation a drug called Cisplatin is used to make the cancer more sensitive to radiotherapy. Chemoradiation has been the main treatment for advanced cervical cancer for the last 25 years.
What is Pembrolizumab?
Pembrolizumab is a type of cancer treatment known as immunotherapy, which helps the body’s immune system fight cancer. It works by blocking a protein called PD-1, found on the surface of certain immune cells called T cells. When PD-1 is blocked, these T cells are activated and can attack and kill cancer cells.
Mechanism of Action of Immunotherapy
KEYNOTE-A18 clinical trial
Pembrolizumab has been effective in treating certain types of cervical cancer, especially when the cancer is persistent, has come back, or has spread to other parts of the body, as the results of a previous trial, the KEYNOTE 826, have suggested. In this study, researchers looked at whether combining pembrolizumab with standard treatments like chemotherapy and radiation (chemoradiotherapy) could improve outcomes for patients with locally advanced cervical cancer. They also evaluated how safe this combination treatment is for patients.
Outcome
In the study, 1,060 patients from 176 medical centers in 30 countries, including locations in Asia, Australia, Europe, North America, and South America, were randomly divided into two groups. Half of the patients received a combination of pembrolizumab and chemoradiotherapy, while the other half received a placebo with chemoradiotherapy.
The results showed that the group receiving pembrolizumab with chemoradiotherapy had significantly better outcomes. The addition of pembrolizumab reduced the risk of disease progression (cancer getting worse) by 32%.
Conclusion
These findings suggest that using pembrolizumab with chemoradiotherapy could become a new standard treatment option for people with locally advanced cervical cancer.
Reference:
1. Lorusso D, Xiang Y, Hasegawa K, Scambia G, Leiva M, Ramos-Elias P, Acevedo A, Sukhin V, Cloven N, Pereira de Santana Gomes AJ, Contreras Mejía F, Reiss A, Ayhan A, Lee JY, Saevets V, Zagouri F, Gilbert L, Sehouli J, Tharavichitkul E, Lindemann K, Lazzari R, Chang CL, Lampé R, Zhu H, Oaknin A, Christiaens M, Polterauer S, Usami T, Li K, Yamada K, Toker S, Keefe SM, Pignata S, Duska LR; ENGOT-cx11/GOG-3047/KEYNOTE-A18 investigators. 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. Lancet. 2024 Apr 6;403(10434):1341-1350. doi: 10.1016/S0140-6736(24)00317-9. Epub 2024 Mar 20. PMID: 38521086.
2. 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): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. (has not been published to PubMed yet)
Link: · https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00317-9/abstract · https://www.sciencedirect.com/science/article/abs/pii/S0140673624018087
