Merck's KEYTRUDA Receives FDA Approval as First Anti-PD-1 Monotherapy for Advanced Esophageal Squamous Cell Carcinoma

Today, MSD announced that the U.S. FDA has approved the company’s blockbuster PD-1 inhibitor Keytruda as a monotherapy for the treatment of patients with recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). These patients have tumors expressing PD-L1 (CPS >10) and have experienced disease progression following one or more prior systemic therapies. Notably, this is the first anti-PD-1 therapy approved for this patient population.

Esophageal cancer typically originates in the inner lining of the esophagus and can extend to other parts of the esophagus and metastasize to other areas of the body. It is primarily classified into two types: squamous cell carcinoma and adenocarcinoma. In 2018, there were over 570,000 newly diagnosed cases of esophageal cancer worldwide, resulting in more than 500,000 deaths. China is one of the countries with the highest incidence rates of esophageal cancer globally. The five-year survival rate for patients at an early stage is 43%; when cancer cells spread to surrounding tissues or organs of the esophagus, the five-year survival rate drops to 23%; if distant metastasis occurs, the patient survival rate is only 5%.

Keytruda is a humanized anti-PD-1 monoclonal antibody therapy developed by MSD. It enhances the body’s immune system to detect and kill cancer cells by blocking the binding of PD-1 to PD-L1 and PD-L2. Since its initial approval in 2014 for the treatment of advanced melanoma, it has been approved for more than 20 indications, including lung cancer, head and neck cancer, gastric cancer, and hepatocellular carcinoma. In China, it has also been approved for the treatment of melanoma and non-squamous non-small cell lung cancer.

This approval is based on the results of the clinical trials named KEYNOTE-181 and KEYNOTE-180. In the open-label, active-controlled, randomized Phase 3 clinical trial KEYNOTE-181, 628 patients with recurrent locally advanced or metastatic esophageal cancer received treatment with Keytruda or chemotherapy. The trial results demonstrated that in patients with esophageal squamous cell carcinoma (ESCC) whose tumors expressed PD-L1 (CPS >10), the median overall survival (OS) was 10.3 months in the Keytruda group compared to 6.7 months in the chemotherapy group (HR=0.64, 95% CI: 0.46, 0.90). The objective response rate (ORR) was 22% in the Keytruda group versus 7% in the chemotherapy group, and the complete response rate (CRR) was 5% versus 1%, respectively. The median duration of response (DOR) was 9.3 months in the Keytruda group and 7.7 months in the chemotherapy group.

In the non-randomized, open-label Phase 2 clinical trial named KEYNOTE-180, 121 patients with locally advanced or metastatic esophageal cancer who had received at least two prior lines of systemic therapy were treated with Keytruda. Among patients with esophageal squamous cell carcinoma (ESCC) whose tumors expressed PD-L1, the objective response rate (ORR) was 20%.

“Treatment options for patients with advanced esophageal cancer are very limited, particularly after their disease has progressed,” said Dr. Jonathan Cheng, Vice President of Oncology Clinical Research at Merck & Co., Inc. Research Laboratories. “With this approval, Keytruda becomes the first anti-PD-1 therapy approved for the treatment of specific patients with previously treated, recurrent locally advanced or metastatic ESCC, providing an important new monotherapy option for patients.”

References:

[1] FDA Approves New Monotherapy Indication for Merck’s KEYTRUDA® (pembrolizumab). Retrieved July 31, 2019, from https://www.mrknewsroom.com/news-release/prescription-medicine-news/fda-approves-new-monotherapy-indication-mercks-keytruda-pemb

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