Phase III Data Show Keytruda’s Promise in Earlier-Stage Cervical Cancer
Pictured: Merck Research Laboratories headquarters in Silicon Valley/iStock, Michael Vi
Though its news release was sparse with specific data from the study, Merck said that an independent Data Monitoring Committee found that Keytruda with chemoradiotherapy led to a significant and clinically meaningful improvement in progression-free survival (PFS), as compared with chemoradiotherapy alone.
“[T]hese results reinforce our research efforts in earlier stages of disease where there is a greater potential for better outcomes,” Gursel Aktan, vice president of global clinical development at Merck Research Laboratories, said in a statement.
KEYNOTE-A18, also known as ENGOT-cx11/GOG-3047, is a randomized and double-blinded trial enrolling 980 patients with newly diagnosed, locally advanced cervical cancer. To be eligible, patients must also be classified as high-risk, defined as having stage 1B2 to 2B and lymph node-positive disease, and stage 3 to 4A cancer regardless of lymph node positivity. Keytruda was administered in combination with external beam radiotherapy and concurrent chemotherapy, followed by brachytherapy.
The study’s two primary endpoints are PFS and overall survival (OS). At the time of the interim analysis, OS data were not yet mature, though Merck documented a favorable trend. The company will continue to follow patients up to collect OS data.
KEYNOTE-A18 documented no new safety signals and Keytruda had an adverse event profile consistent with what had previously been observed.
Merck will file these findings for presentation at an upcoming medical congress and will present these earlier-stage cervical cancer data to regulatory bodies. Keytruda, a humanized monoclonal antibody designed to disrupt the interaction between the PD-1 receptor and its ligands, was first approved in 2014 for advanced melanoma.
Keytruda’s mechanism of action allows it to prevent the cascade that cancer cells use to hide from the immune system. As a result, Keytruda enables the body’s T lymphocytes to target and destroy tumor cells.
The PD-1 blocker picked up its first cervical cancer in 2018. In this indication, Keytruda is authorized as a combination treatment with chemotherapy, with or without Roche’s Avastin (bevacizumab), for persistent, recurrent or metastatic disease. Keytruda can also be given as a single agent to metastatic or recurrent cervical cancer patients who had progressed on or after chemotherapy.
In both cases, patients need to be positive for PD-L1 expression, as determined by an FDA-approved test.
Keytruda can now add Wednesday’s cervical cancer win to its growing list of approvals and impressive clinical wins this year, which includes FDA nods in adjuvant non-small cell lung cancer and first-line urothelial carcinoma, as well as a promising Phase III performance in biliary tract cancer.