FDA Approves Merck’s KEYTRUDA® Plus Platinum Chemotherapy as First-Line Anti-PD-1 Combination Therapy for Cervical Cancer, Significantly Improving Survival

October 13, 2021 /BioonBIOON/ -- MSD (Merck & Co.) recently announced that the U.S. Food and Drug Administration (FDA) has approved the anti-PD-1 therapy Keytruda® (pembrolizumab) in combination with platinum-based chemotherapy (with or without bevacizumab), forFirst-line treatment viaFDAConfirmed by the approved test method asTumorPD-L1–positive (Combined Positive Score [CPS] ≥ 1) persistent, recurrent, or metastatic cervical cancerPatient. It is worth noting that,This is the first anti-PD-1 combination therapy approved for first-line treatment of these patients.。Data from the pivotal Phase 3 KEYNOTE-826 trial (NCT03635567) show:Compared with chemotherapy, first-line treatment with Keytruda + chemotherapy (± bevacizumab) significantly reduced the risk of death by 36%.

Cervical cancer remains the second leading cause of cancer-related death among young women aged 15–44 years, and historically, women at an advanced stageDiagnosisPrognosis is poor. Over the past 7 years, no first-line treatment has been approved for persistent, recurrent, or metastatic cervical cancer.Keytruda is the first anti-PD-1/PD-L1 therapy to improve overall survival when used in combination with platinum-based chemotherapy (with or without bevacizumab) as first-line treatment for patients with persistent, recurrent, or metastatic cervical cancer.。With this latest approval, Keytruda + platinum-based chemotherapy (± bevacizumab) will provide a new first-line treatment option for these patients.

In June 2018, based on tumor response data from the Phase 2 KEYNOTE-158 trial,FDAAccelerated Approval of Keytruda: as a monotherapy for the treatment of disease progression during or following prior chemotherapy, andTumorPatients with recurrent or metastatic cervical cancer expressing PD-L1 (CPS ≥ 1). The Phase 3 KEYNOTE-826 trial is the confirmatory trial for the accelerated approval of Keytruda for the treatment of cervical cancer. Based on the confirmatory data from the KEYNOTE-826 trial,FDAThis accelerated approval has now been converted to regular approval.

Despite advances in prevention and screening, cervical cancer remains a significant health concern, often affecting young and middle-aged women. The prognosis for women diagnosed with metastatic cervical cancer is particularly poor, underscoring an urgent need for new treatment options. KEYNOTE-826 is the first study to demonstrate positive results with immunotherapy in the first-line setting for persistent, recurrent, or metastatic cervical cancer.

The KEYNOTE-826 trial evaluated the efficacy and safety of Keytruda versus placebo, in combination with platinum-based chemotherapy (paclitaxel plus cisplatin, or paclitaxel plus carboplatin) with or without bevacizumab, as first-line treatment in 617 adult patients with persistent, recurrent, or metastatic cervical carcinoma (including squamous cell carcinoma, adenosquamous carcinoma, and adenocarcinoma) who had not previously received systemic chemotherapy and were no longer candidates for curative therapy (e.g., surgery and/or radiotherapy). The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety.

The results showed that,InTumorIn PD-L1–expressing patients (CPS ≥ 1): Compared with placebo + chemotherapy (± bevacizumab), Keytruda + chemotherapy (± bevacizumab) improved OS, PFS, ORR, and DOR. Results were consistent regardless of bevacizumab use.

The specific data are as follows: (1) OS: Compared with placebo + chemotherapy (± bevacizumab), Keytruda + chemotherapy (± bevacizumab) reduced the risk of death by 36% (HR = 0.64 [95% CI: 0.50–0.81]; p = 0.0001). (2) PFS: Compared with placebo + chemotherapy (± bevacizumab), Keytruda + chemotherapy (± bevacizumab) reduced the risk of disease progression or death by 38% (HR = 0.62 [95% CI: 0.50–0.77]; p < 0.0001). (3) ORR: The Keytruda + chemotherapy (± bevacizumab) group showed an ORR of 68% (95% CI: 62–74), while the placebo + chemotherapy (± bevacizumab) group showed an ORR of 50% (95% CI: 44–56). (4) DOR: The median DOR in the Keytruda + chemotherapy (± bevacizumab) group was 18.0 months (range: 1.3+ to 24.2+ months), and the DOR in the placebo + chemotherapy (± bevacizumab) group was 10.4 months (range: 1.5+ to 22.0+ months). In this trial, the safety profile of Keytruda was consistent with that reported in previous studies.

Cervical cancer is the fourth leading cause of cancer death among women worldwide. Although it can occur in women of any age, it is most commonly diagnosed in women aged 35–44. Nearly all cases are caused by human papillomavirus (HPV) infection. Approximately 80% are classified as squamous cell carcinoma (SCC), which originates from the cells in the lower part of the cervix, while the majority of the remaining cases are adenocarcinomas, which arise from the glandular cells in the upper part of the cervix.

Despite advances in routine medical screening and prevention (HPV vaccination), cervical cancer remains prevalent. It is estimated that worldwide, over 600,000 new cases of cervical cancer are diagnosed annually, resulting in more than 340,000 deaths. Cervical cancer is typically curable when detected early and treated effectively, but treatment options for advanced, recurrent, or metastatic cervical cancer are limited, and survival rates are very low. In the United States, for# DiagnosisFor patients with cervical cancer that has spread to distant parts of the body, the 5-year survival rate is estimated to be approximately 17%.

Keytruda is a PD-(L)1 tumor immunotherapy that enhances the human immune system's ability to detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T lymphocytes that may affectTumorT lymphocytes of cells and healthy cells.

To date, globally, more than 10 PD-(L)1 cancer immunotherapies have been approved, with Keytruda leading the field. MSD operates the largest immuno-oncology clinical development program in the industry, currently comprising over 1,600Clinical TrialInvestigating Keytruda in multiple types ofTumorand its role in the treatment setting. The Keytruda clinical program is designed to understand the drug's role in cancer and factors that may predict patient benefit from Keytruda treatment, including exploring several differentBiomarker. (Bioon.com)

Original source:FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy, With or Without Bevacizumab, as Treatment for Patients With Persistent, Recurrent or Metastatic Cervical Cancer Whose Tumors Express PD-L1 (CPS ≥1)