Merck's Keytruda Recommended by NICE for First-Line Esophageal Cancer Treatment and Covered by NHS

Compiled and Translated by | Fan Dongdong

Recently, the UK's National Institute for Health and Care Excellence (NICE) has recommended MSD's blockbuster oncology drug Keytruda (pembrolizumab) in combination with chemotherapy as a first-line treatment for certain patients with esophageal cancer. Eligible UK patients will be able to access this treatment directly through the National Health Service (NHS) in the future.

Specifically, the UK's NICE has now approved Keytruda in combination with platinum- and fluoropyrimidine-based chemotherapy as a treatment option for adult patients in the UK with untreated unresectable or metastatic esophageal cancer, or PD-L1-positive, HER2-negative adenocarcinoma of the gastroesophageal junction. In March 2021, the U.S. Food and Drug Administration (FDA) approved MSD's Keytruda (pembrolizumab) in combination with platinum- and fluoropyrimidine-based chemotherapy for the same indication.

Following its approval, the drug became the first novel immunotherapy available to this patient population in the UK via the NHS. Keytruda is a PD-(L)1 tumor immunotherapy and a humanized monoclonal antibody that primarily works by blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T lymphocytes that may affect both tumor cells and healthy cells. This therapy enhances the body's immune system, helping patients detect and combat tumor cells.

Regarding the inclusion of this drug in the UK's National Health Service (NHS), Was Mansoor, Consultant Medical Oncologist at an NHS Foundation Trust, stated that advanced oesophageal cancer is highly aggressive, and current treatment options are very limited, offering only modest clinical benefit to patients. Over the past half-century, there has been an urgent need in the UK to improve treatment options for these patients, and NICE’s approval of pembrolizumab represents a significant step forward in addressing these needs.

The recent NICE approval of this drug was primarily based on positive results from a prior Phase III trial. KEYNOTE-590 (NCT03189719) was a multicenter, randomized, placebo-controlled trial that enrolled 749 patients with metastatic or locally advanced esophageal or gastroesophageal junction (GEJ) cancer who were ineligible for surgical resection or chemoradiotherapy, to evaluate the efficacy of chemotherapy combined with pembrolizumab. Patients were randomized 1:1 to receive either pembrolizumab plus cisplatin and fluorouracil, or placebo plus cisplatin and fluorouracil. Treatment continued until unacceptable toxicity or disease progression precluded further therapy.

The trial results demonstrated statistically significant improvements in overall survival (OS) and progression-free survival (PFS) in both groups of subjects. The median overall survival was 12.4 months in the pembrolizumab treatment group, compared with 9.8 months in the chemotherapy group. The median progression-free survival was 6.3 months in the pembrolizumab treatment group, compared with 5.8 months in the chemotherapy group. In the KEYNOTE-590 trial, the most commonly reported adverse events (≥20%) among patients receiving pembrolizumab in combination with chemotherapy were nausea, constipation, diarrhea, vomiting, stomatitis, fatigue, decreased appetite, and weight loss.

Esophageal cancer is often already fatal by the time patients are typically diagnosed at stage III or stage IV. Unlike other cancers, patients have virtually no novel therapeutic options in clinical practice, making it one of the "most difficult cancers to survive."

To date, more than 10 PD-(L)1 oncology immunotherapies have been approved globally, yet MSD's Keytruda continues to maintain a leading position in this field. In 2020, global sales of the therapy reached $14.38 billion, representing a 30% year-on-year increase. Notably, in early September this year, the drug received approval from China's National Medical Products Administration (NMPA) for the same indication, making Keytruda the first anti-PD-1 regimen approved in mainland China for the first-line treatment of advanced esophageal cancer or gastroesophageal junction (GEJ) cancer.

Source: Keytruda made available on the NHS for certain oesophageal cancer patients