Merck's KEYTRUDA® (pembrolizumab) Plus Chemotherapy Approved by European Commission as First-Line Treatment for Esophageal Cancer and HER2-Negative GEJ Adenocarcinoma

Esophageal cancer (Image source: medindia.net)

June 29, 2021 /BioonBIOON/ -- MSD (Merck & Co.) recently announced that the European Commission (EC) has approved the anti-PD-1 therapy Keytruda (generic name: pembrolizumab), in combination with chemotherapy (platinum plus fluoropyrimidine), as a first-line treatmentTumorAdult patients with PD-L1–expressing (combined positive score [CPS] ≥10) locally advanced unresectable or metastatic esophageal cancer or HER2-negative gastroesophageal junction (GEJ) adenocarcinoma.

Notably,Keytruda is the first PD-1 therapy approved in Europe for the first-line treatment of advanced esophageal or gastroesophageal junction (GEJ) cancer in combination with chemotherapy, regardless of histology.。This approval will change the current first-line treatment paradigm for these patients.. In the pivotal Phase 3 KEYNOTE-590 trial,Regardless of histology or PD-L1 expression status, Keytruda plus chemotherapy significantly prolonged overall survival (OS) and progression-free survival (PFS) compared with chemotherapy.

In March this year, Keytruda + chemotherapy (platinum + fluoropyrimidine) received U.S.FDAApproved for the first-line treatment of patients with metastatic or locally advanced esophageal or GEJ adenocarcinoma who are not candidates for surgical resection or definitive radiotherapy. In China, Keytruda is approved as a monotherapy for second-line treatmentTumorPatients with recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) expressing PD-L1 (CPS ≥ 10). Currently, through its extensive clinical development program, MSD continues to evaluate 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, among others.

Montpellier Cancer Research Institute (IRCM)TumorProfessor Antoine Adenis, Internal Medicine, stated: "Over the past 30 years, we have rarely seen advances that improve the historically poor survival outcomes for patients with esophageal cancer. The European Commission's approval of Keytruda in combination with chemotherapy for the treatment of certain patients with esophageal cancer and HER2-negative GEJ cancer provides a new first-line treatment option that has demonstrated significant improvements in both progression-free survival and overall survival."

Dr. Scot Ebbinghaus, Vice President of Clinical Research, MSD Research Laboratories, stated: “Keytruda in combination with chemotherapy is the first anti-PD-1 therapy approved in Europe for the first-line treatment of patients with locally advanced, unresectable, or metastatic esophageal or GEJ cancer, enabling these patients to receive immunotherapy earlier in their treatment course to improve survival outcomes.”

KEYNOTE-590 Trial: Results in the Overall Population

This EU approval is based on data from the pivotal Phase 3 KEYNOTE-590 trial (NCT03189719). The trial evaluated Keytruda in combination with chemotherapy (cisplatin + 5-fluorouracil [5-FU]) as first-line treatment for patients with locally advanced unresectable or metastatic esophageal and gastroesophageal junction (GEJ) cancer.

Data shows,In the overall study population (intent-to-treat [ITT] population), regardless of histology or PD-L1 expression status,, compared with chemotherapy, Keytruda + chemotherapy: (1)Significantly prolongs overall survival(median OS: 12.4 months vs. 9.8 months), reducing the risk of death by 27% (HR = 0.73; 95% CI: 0.62–0.86; p < 0.0001); (2)Significantly prolong progression-free survival (Median PFS: 6.3 months vs. 5.8 months), reduced the risk of disease progression or death by 35% (HR = 0.65; 95% CI: 0.55–0.76; p < 0.0001); (3)Significantly improve the objective response rate(ORR: 45.0% vs 29.3%), prolonged the duration of response (median DOR: 8.3 months vs 6.0 months).

InTumorPD-L1–expressing patients (CPS ≥ 10) (n=383/749)In the prespecified analysis conducted, compared with chemotherapy, Keytruda plus chemotherapy: (1)Significantly Prolongs Overall Survival(median OS: 13.5 months vs. 9.4 months), representing a 38% reduction in the risk of death (HR=0.62; 95% CI: 0.49-0.78; p<0.0001); (2)Significantly Prolongs Progression-Free Survival(median PFS: 7.5 months vs. 5.5 months), reduced the risk of disease progression or death by 49% (HR = 0.51; 95% CI: 0.41–0.65; p < 0.0001); (3)Significantly improve the objective response rate(ORR: 51.1% vs 26.9%), prolonged the duration of response (median DOR: 10.4 months vs 5.6 months). In this study, the safety profile of Keytruda was consistent with that reported in previous studies.

Esophageal cancer is an aggressive and devastating malignancy with a high mortality rate, leaving few treatment options beyond chemotherapy. For newDiagnosis, previously untreated patients urgently require therapeutic advances. According to the results of the KEYNOTE-590 trial,Keytruda is the first anti-PD-1 therapy to demonstrate superior OS, PFS, and ORR compared with current standard-of-care chemotherapy when combined with chemotherapy as first-line treatment for esophageal cancer, regardless ofTumorWhat is the histology or PD-L1 expression status.

Esophageal cancer is a particularly difficult-to-treat cancer that originates in the inner layer (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 commonDiagnosiscancer, and is also the sixth leading cause of cancer death. It is estimated that in 2018, there were over 572,000 new cases of esophageal cancer worldwide, with nearly 509,000 deaths. In China, esophageal cancer is the fifth most common cancer and the fourth leading cause of cancer death, with 90% of cases being squamous cell carcinoma.

Keytruda is a PD-(L)1 cancer immunotherapy that helps detect and combat tumor cells by enhancing the capabilities of the human 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 that may affectTumorT lymphocytes of cells and healthy cells.

To date, globally, there are already more than 10 PD-(L)1TumorImmunotherapies have gained market approval, with Keytruda emerging as the leader in this field. Approved for multiple therapeutic indications, its global sales reached $14.38 billion in 2020, representing a 30% year-on-year increase.

MSD has the largest immuno-oncology clinical development program in the industry, with currently over 1,500Clinical TrialCurrently investigating Keytruda in multiple typesTumorand its role in the therapeutic context. The Keytruda clinical program aims to understand the drug's role in cancer and factors that may predict patient benefit from Keytruda treatment, including exploring several differentBiomarker.(Bioon.com)

Source:European Commission Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy for Certain Patients With Esophageal Cancer or HER2-Negative Gastroesophageal Junction (GEJ) Adenocarcinoma