Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Achieves Major Success in Phase III First-Line Treatment of Esophageal Cancer

August 20, 2020 /BioValleyBIOON/ -- Merck & Co. recently announced that the pivotal Phase III KEYNOTE-590 trial, evaluating the first-line treatment of locally advanced or metastatic esophageal cancer with the anti-PD-1 therapy Keytruda (pembrolizumab) in combination with chemotherapy (cisplatin plus 5-fluorouracil [5-FU]), met both primary endpoints of overall survival (OS) and progression-free survival (PFS).

KEYNOTE-590 is a randomized, double-blind Phase III trial (NCT03189719) that enrolled a total of 749 patients with locally advanced or metastatic esophageal cancer (esophageal adenocarcinoma or squamous cell carcinoma, or Siewert type 1 adenocarcinoma of the esophagogastric junction). In this study, patients were randomly assigned to receive Keytruda plus chemotherapy or placebo plus chemotherapy as first-line therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS), while secondary endpoints included overall response rate (ORR), duration of response (DOR), and safety.

According to the interim analysis conducted by the Independent Data Monitoring Committee, the Keytruda plus chemotherapy group demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared with the placebo plus chemotherapy group in the intent-to-treat (ITT) population. Furthermore, the study met its key secondary endpoint: the objective response rate (ORR) was significantly higher in the Keytruda plus chemotherapy group than in the placebo plus chemotherapy group. The safety profile of Keytruda in this study was consistent with that reported in previous studies.

It is worth mentioning that,Keytruda is the first anti-PD-1 therapy to demonstrate superior survival benefits in the first-line treatment of esophageal cancer in combination with chemotherapy, regardless of histology.The results of the KEYNOTE-590 study will be shared with global regulatory authorities and have been submitted to the 2020 EuropeanTumorEuropean Society for Medical Oncology (ESMO) VirtualMeetingIntroduction.

Currently,Keytruda is approved in the United States and China as a monotherapy for second-line treatmentTumorPatients with recurrent locally advanced or metastatic esophageal squamous cell carcinoma expressing PD-L1 (Combined Positive Score [CPS] ≥ 10).

Esophageal Cancer (Image source: medindia.net)

MSD is continuing to investigate the therapeutic potential of Keytruda across multiple settings and stages of gastrointestinal cancers, including gastric cancer, hepatobiliary cancer, esophageal cancer, pancreatic cancer, colorectal cancer, and anal canal cancer, through its extensive clinical program.

“Esophageal cancer is a devastating malignancy,” said Dr. Roy Baynes, Senior Vice President of Merck Research Laboratories, Global Head of Clinical Development, and Chief Medical Officer.Tumor, with a high mortality rate and few treatment options other than chemotherapy. In this pivotal study, Keytruda in combination with chemotherapy demonstrated superior overall survival compared to the current standard of care across the entire study population and all evaluated patient subgroups. These results build upon our existing research, further reinforcing the survival benefit of Keytruda, and we look forward to engaging with regulatory authorities as soon as possible.”

Esophageal cancer is a particularly difficult-to-treat malignancy that originates in the inner lining (mucosa) of the esophagus and grows outward. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. Globally, esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of cancer-related death. It is estimated that in 2018, there were over 572,000 new cases of esophageal cancer worldwide, with nearly 509,000 deaths. In the United States, in 2020, newDiagnosis18,500 cases of esophageal cancer, with 16,000 deaths from the disease. In China, esophageal cancer is the fifth most common cancer and the fourth leading cause of cancer-related death; 90% of esophageal cancers are squamous cell carcinomas.

Keytruda is a PD-(L)1 cancer immunotherapy that helps detect and fight tumor cells by enhancing the body’s immune system. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T cells that may affectTumorT lymphocytes of cells and healthy cells.

To date, more than 10 PD-(L)1TumorImmunotherapy Approved for Market Launch: Keytruda Leads the Field with Over 20 Approved Indications, Achieving Global Sales of $11.1 Billion in 2019, a 58% Year-on-Year Increase

MSD has the largest immuno-oncology clinical development program in the industry, with more than 1,200 ongoing trials.Clinical TrialsInvestigating Keytruda in multiple typesTumorand its role in the treatment context. The Keytruda clinical program aims to understand the drug’s role in cancer and identify factors that may predict patient benefit from Keytruda therapy, including exploring several differentBiomarker(Bioon.com)

Original Source: Merck’s KEYTRUDA® (pembrolizumab) in Combination With Chemotherapy Significantly Improved Overall Survival and Progression-Free Survival Compared With Chemotherapy in Locally Advanced or First-Line Metastatic Esophageal Cancer