Phase III KEYNOTE-A18 Trial Data Show Keytruda Plus Chemoradiotherapy Improves Overall Survival in High-Risk Cervical Cancer

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Results from the Phase III KEYNOTE-A18 trial (NCT04221945) show that Merck’s Keytruda (pembrolizumab) plus chemoradiotherapy achieved the study’s primary endpoint of overall survival (OS) in patients newly diagnosed with high-risk locally advanced cervical cancer.¹ These data follow the January FDA approval of Keytruda plus chemoradiation for patients with FIGO 2014 stage III to IVA cervical cancer, which was the third approval for Keytruda for cervical cancer and the 39th overall approved indication for the drug in the United States.²

“This is the first Phase III trial in which an immunotherapy-based regimen has shown a statistically significant and clinically meaningful improvement in (OS) compared to chemoradiotherapy alone,” Gursel Aktan, MD, PhD, vice president, global clinical development, Merck Research Laboratories, said in a press release. “Building on the positive progression-free survival (PFS) findings from this study, 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.”¹

Last year, data from KEYNOTE-A18 showed that the anti-PD-1 therapy combined with external beam radiotherapy (EBRT) plus concurrent chemotherapy, followed by concurrent chemoradiotherapy, achieved one of the trial’s primary endpoints of PFS.³

The randomized, double-blind, KEYNOTE-A18 trial evaluated Keytruda with cisplatin and EBRT followed by concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in newly diagnosed patients with stage IB2-IIB lymph node-positive locally advanced cervical cancer, and patients with stage III-IVA with and without lymph node-positive, locally advanced cervical cancer, in which patients were treated with definitive intent. In addition to the primary endpoints of PFS and OS, secondary endpoints included complete response rate, objective response rate, and safety.

Investigators enrolled 1,060 patients with cervical cancer who were not previously treated with any definitive surgery, radiation, or systemic therapy for cervical cancer. Patients were randomly assigned at 1:1 ratio to receive either Keytruda at a dose of 200 mg intravenously (IV) every three weeks for five cycles concurrent with cisplatin at a dose of 40 mg/m² IV weekly for five cycles and radiotherapy with EBRT followed by concurrent chemoradiotherapy, followed by Keytruda 400 mg IV every six weeks for 15 cycles; or placebo IV every three weeks for five cycles concurrent with cisplatin 40 mg/m² IV weekly for five cycles and EBRT followed by concurrent chemoradiotherapy, followed by placebo IV every six weeks for 15 cycles.

A prespecified interim analysis conducted by an independent Data Monitoring Committee showed the Keytruda combination produced a statistically significant and clinically meaningful improvement in PFS compared with concurrent chemoradiotherapy alone.³

“These findings are important for patients and the medical community alike and reinforce previous data from the KEYNOTE-A18 trial, now showing this regimen has the potential to extend the lives of patients with locally advanced cervical cancer,” KEYNOTE-A18 trial overall principal investigator, Domenica Lorusso, lead investigator for ENGOT and professor of Obstetrics and Gynecology at Humanitas University, said in a press release.¹

References

1. Merck’s KEYTRUDA® (pembrolizumab) Plus Chemoradiotherapy (CRT) Significantly Improved Overall Survival (OS) Versus CRT Alone in Patients With Newly Diagnosed High-Risk Locally Advanced Cervical Cancer. Merck. News release. March 15, 2024. Accessed March 15, 2024. https://www.merck.com/news/mercks-keytruda-pembrolizumab-plus-chemoradiotherapy-crt-significantly-improved-overall-survival-os-versus-crt-alone-in-patients-with-newly-diagnosed-high-risk-locally-advanced-ce/

2. 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 March 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/

3. Merck Announces Phase 3 KEYNOTE-A18 Trial Met Primary Endpoint of Progression-Free Survival (PFS) in Patients With Newly Diagnosed High-Risk Locally Advanced Cervical Cancer. Merck. News release. July 19, 2023. Accessed March 15, 2024. https://www.merck.com/news/merck-announces-phase-3-keynote-a18-trial-met-primary-endpoint-of-progression-free-survival-pfs-in-patients-with-newly-diagnosed-high-risk-locally-advanced-cervical-cancer/