Merck's Keytruda Receives Third FDA Approval for Cervical Cancer

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The FDA has approved Merck’s Keytruda (pembrolizumab) combined with chemoradiation for the treatment of patients with FIGO 2014 stage III to IVA cervical cancer. The regulatory action is the third approval for Keytruda for the treatment of cervical cancer and the 39th overall approved indication for the drug in the United States.

“[The] approval of Keytruda plus chemoradiotherapy is welcome news and gives patients with newly diagnosed FIGO 2014 Stage III-IVA cervical cancer, for the first time ever, the option of an anti-PD-1-based regimen to treat their cancer,” Bradley Monk, MD, oncologist and professor of obstetrics and gynecology at University of Arizona College of Medicine and Creighton University School of Medicine, said in a press release. “This Keytruda-based regimen offers a new treatment option for these patients, so today’s approval has important implications for the way we treat them moving forward.”

Keytruda is an anti-programed death receptor-1 (PD-1) therapy that improves the immune system's ability to detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which leads to the activation of T lymphocytes that could affect tumor and healthy cells.

The latest approval for the drug was based on safety and efficacy data from the multicenter, randomized, double-blind, placebo-controlled Phase III KEYNOTE-A18 trial (NCT04221945). The study found that Keytruda plus chemoradiation produced a significant improvement in progression-free survival (PFS) compared with placebo in the overall patient population. Investigators enrolled approximately 1060 patients with cervical cancer who had not undergone definitive surgery or prior radiation or systemic treatment.

Patients enrolled in the trial were randomly assigned 1:1 to receive 200 mg of pembrolizumab intravenously or placebo every three weeks for five cycles plus chemoradiation followed by 400 mg of pembrolizumab or placebo every six weeks for 15 total cycles. The chemoradiation regimen was 40 mg/m² of cisplatin administered weekly for five cycles with an optional sixth cycle plus external beam radiation therapy (EBRT) and brachytherapy. Treatment continued until disease progression by RECIST v1.1 criteria definition and investigator assessment or intolerable toxicity.

In a subset of patients with FIGO 2014 stage III to IVA disease, the median age was 52 years (range, 22-87), with 17% of patients 65 years of age or older. Further, 38% of patients were Hispanic or Latino, 36% of patients were White, 34% were Asian, and 1% were Black.

The major efficacy outcomes for KEYNOTE-A18 included investigator-assessed PFS by RECIST v1.1 criteria, modified to follow up to 10 target lesions and up to five target lesions per organ, or histopathologic confirmation, and OS.

Data from an exploratory subgroup showed a hazard ratio (HR) of 0.59 (95% CI, 0.43-0.82) for PFS in a subset of patients with FIGO 2014 stage III to IVA disease (n = 596). Further, 21% of patients in the Keytruda cohort experienced a PFS event compared with 31% of patients in the placebo cohort. Median PFS was not reached (NR) in both the Keytruda cohort (95% CI, NR-NR) and the placebo cohort (95% CI, 18.8-NR). Twelve-month PFS rates were 81% in the Keytruda cohort (95% CI, 75%-85%) compared with 70% (95% CI, 64%-76%) in the placebo cohort.

Patients with FIGO 2014 stage IB2 to IIB disease (n = 462) showed an estimated HR for PFS of 0.91 (95% CI, 0.63-1.31). The FDA noted that the PFS improvement in the overall population was primarily attributable to the subset of patients with stage III to IV disease. Overall survival data were not yet mature at the time of the PFS analysis.

“Building on the established role of Keytruda in advanced cervical cancer, Keytruda plus chemoradiotherapy is now the first anti-PD-1-based regimen approved in the US for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer regardless of PD-L1 expression,” said Gursel Aktan, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “This approval provides newly diagnosed patients with an anti-PD-1-based treatment option that has the potential to reduce the risk of disease progression or death compared to chemoradiotherapy alone.”

Reference

FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemoradiotherapy as Treatment for Patients With FIGO 2014 Stage III-IVA Cervical Cancer. Merck. News release. January 12, 2024. Accessed January 15, 2024. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-chemoradiotherapy-as-treatment-for-patients-with-figo-2014-stage-iii-iva-cervical-cancer/