Two months after Keytruda became the first PD-1 drug to be approved in the United States in combination with chemoradiotherapy (CRT) to treat patients with stage 3 to 4a cervical cancer, Merck’s superstar immunotherapy has strengthened its resume in the indication.
A pre-specified interim analysis from the KEYNOTE-A18 trial found that the combo regimen significantly improved overall survival (OS) versus CRT alone in patients with earlier-stage cervical cancer, the company reported on Friday.
In meeting its primary endpoint of OS for the treatment of newly diagnosed patients with high-risk locally advanced cervical cancer, Keytruda could be set up for approval for a broader population in the indication. It is the first immunotherapy-based regimen to demonstrate a statistically significant improvement in keeping these patients alive longer.
Detailed results will be revealed at an upcoming medical conference and will be shared with regulators worldwide, Merck said.
Overall survival was one of two primary endpoints in KEYNOTE-A18. The other was progression-free survival (PFS), which the company reported last year and set up the January FDA endorsement.
That OK, however, was narrower than expected. In the trial overall, which included patients whose cancer was as early as stage 1b2, Keytruda plus CRT cut the risk of tumor progression or death by 30%. But the benefit was more pronounced in those with stage 3 to 4a disease at 41%, compared to just 9% in those with stage 1b2 to 2b disease.
After reviewing those results, the FDA doled out the approval to patients with stage 3 to 4a disease.
The question now is how the subgroup analysis falls out in OS.
“These results underscore our commitment to exploring the role of Keytruda across different types of cancers in earlier stages of disease where there is a greater potential for better outcomes,” Gursel Aktan, Merck’s VP of global clinical development, said in a release.
Keytruda's first full FDA approval in the indication came in October 2021, when it was endorsed in combination with chemotherapy for treating patients with persistent, recurrent or metastatic cervical cancer. The approval allowed the combo to be used with or without Roche's Avastin. But it included a restriction that limited the combo to those whose tumors express the PD-L1 biomarker at a combined positive score (CPS) of at least 1.
That approval converted a 2018 accelerated nod which allowed Keytruda to be used as a solo agent for cervical cancer with disease progression on or after chemotherapy in patients with PD-L1 CPS of at least 1.
The January nod was the 39th for Keytruda, which generated sales of $25 billion last year, making it highest selling pharmaceutical product in 2023 as it surpassed Pfizer and BioNTech’s COVID-19 vaccine Comirnaty, which led the way in 2021 and 2022.
Keytruda also pulled in front of long-time leader, AbbVie’s Humira, as that medicine began to face biosimilar competition in the U.S. Humira was the world’s top seller from 2012 to 2020.