Approval

China NMPA Approves Mercks Keytruda In Combo With Chemotherapy To Treat Locally Advanced Unresectable Or Metastatic Esophageal GEJ Carcinoma

September 10,2021 09:52 AM
- By Admin

Merck announced that Keytruda, Merck’s anti-PD-1 therapy, has been approved by the National Medical Products Administration (NMPA) in China in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus or gastroesophageal junction (GEJ). This new indication was granted approval based on overall survival (OS) findings from the pivotal phase 3 KEYNOTE-590 trial. Keytruda is now approved for eight indications across five different types of cancer in China.

“In China, esophageal and gastroesophageal junction cancers are leading causes of death, and there have been few treatment advances for patients over the past several decades,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “With this approval of Keytruda plus chemotherapy – the first for an anti-PD-1 regimen in the first-line setting – we can now provide patients with an immunotherapy treatment option earlier in the course of treatment that has been shown to significantly improve survival.”

In the global KEYNOTE-590 study, Keytruda in combination with chemotherapy (5-fluorouracil [5-FU] plus cisplatin) demonstrated statistically significant improvements in OS and progression-free survival (PFS) compared with 5-FU and cisplatin alone. Keytruda plus 5-FU and cisplatin reduced the risk of death by 27% (HR=0.73 [95% CI, 0.62-0.86]; p<0.0001). The median OS was 12.4 months (95% CI, 10.5-14.0) for patients treated with Keytruda plus 5-FU and cisplatin and 9.8 months (95% CI, 8.8-10.8) for patients treated with 5-FU and cisplatin alone. Keytruda plus 5-FU and cisplatin reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.55-0.76]; p<0.0001). The median PFS was 6.3 months (95% CI, 6.2-6.9) for patients treated with Keytruda plus 5-FU and cisplatin and 5.8 months (95% CI, 5.0-6.0) for patients treated with 5-FU and cisplatin alone in all randomized patients. The Chinese package insert notes that the safety of Keytruda plus chemotherapy was investigated in 51 Chinese patients with esophageal carcinoma in KEYNOTE-590, and the safety profile of the Chinese patients was generally consistent with the known safety profiles of Keytruda monotherapy and chemotherapy.

“Compared to the rest of the world, China has a disproportionate number of patients who are diagnosed with and who die from esophageal cancer, the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in the country,” said Prof. Shen Lin, vice president, Clinical Oncology, Beijing Cancer Hospital and Peking University, and deputy director, Beijing Institute for Cancer Research. “This approval for Keytruda provides an important new option to patients with advanced esophageal carcinoma in China who currently have limited available treatment options in the first-line setting.”

“We are thrilled to bring this new Keytruda combination treatment option, which has shown significant improvements in progression-free and overall survival, to esophageal cancer patients in China,” said Anna Van Acker, president, MSD China. “We continue to work with urgency to address the unmet needs of patients in China through our broad global clinical program, and we are committed to working with stakeholders to ensure patient access.”

This is the second indication for Keytruda in esophageal cancer in China. In addition to this new approval, Keytruda is approved in China for a second-line treatment of certain patients with locally advanced or metastatic esophageal squamous cell carcinoma whose tumors express PD-L1 (Combined Positive Score [CPS] =10). Merck is continuing to study Keytruda across multiple settings and stages of gastrointestinal cancer through its broad clinical program, including studies in esophageal, gastric, hepatobiliary, pancreatic, colorectal and anal cancers.

KEYNOTE-590 is a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 749 patients with locally advanced unresectable or metastatic esophageal or GEJ carcinoma (Siewert type I) who were not candidates for surgical resection or definitive chemoradiation. Patients were randomized (1:1) to receive either Keytruda (200 mg on Day 1 every three weeks) or placebo (on Day 1 every three weeks) in combination with cisplatin (80 mg/m2 on Day 1 every three weeks for up to six cycles) plus 5-FU (800 mg/m2 per day on Days 1 to 5 every three weeks, or per local standard for 5-FU administration, for up to 24 months); all study medications were administered via intravenous infusion.

Esophageal cancer begins in the inner layer (mucosa) of the esophagus and grows outward. Worldwide, esophageal cancer is the eighth most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide.

Keytruda is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help 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 which may affect both tumor cells and healthy cells.