Merck’s KEYTRUDA® Plus Trastuzumab and Chemotherapy Significantly Improves Overall Survival in HER2-Positive Advanced Gastric or GEJ Cancer
Monday, September 16, 2024
Merck has announced new overall survival results from the final analysis of the Phase 3 KEYNOTE-811 trial.
KEYTRUDA is an anti-PD-1 therapy that helps the immune system fight tumour cells by blocking PD-1 interactions. It is a humanised monoclonal antibody that activates T lymphocytes.
Gastric cancer grows slowly and often goes undetected until advanced. Most cases are adenocarcinomas from the stomach's lining. It’s the fifth most common cancer and cause of cancer deaths globally, with around 969,000 new cases and 660,000 deaths in 2022. In the U.S., 26,890 cases are expected in 2024, with 10,880 deaths. The five-year survival rate for advanced-stage gastric cancer is just 7%.
This study evaluated KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, combined with trastuzumab, fluoropyrimidine-, and platinum-based chemotherapy, as a first-line treatment for adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
The data is being presented at the European Society for Medical Oncology (ESMO) Congress 2024 and published simultaneously in the New England Journal of Medicine.
After a median follow-up of 50.2 months, the KEYTRUDA regimen showed a significant and clinically relevant improvement in overall survival (OS) for the intention-to-treat (ITT) population with HER2-positive advanced gastric or GEJ cancer.
The risk of death was reduced by 20% (HR=0.80 [95% CI, 0.67-0.94]; p=0.0040 [p-value bound 0.0201]) compared to trastuzumab and chemotherapy alone. The median OS for patients receiving the KEYTRUDA regimen was 20.0 months, compared to 16.8 months for those receiving trastuzumab plus chemotherapy.
Additionally, the KEYTRUDA regimen showed a meaningful improvement in OS for patients with PD-L1 expressing tumours (Combined Positive Score [CPS] ≥1), reducing the risk of disease progression or death by 21% (HR=0.79 [95% CI, 0.66-0.95]) compared to trastuzumab and chemotherapy alone.
The median OS was 20.1 months for patients with PD-L1 positive tumours receiving the KEYTRUDA regimen, compared to 15.7 months for those on trastuzumab and chemotherapy alone. Notably, 85% of patients’ tumours in the study expressed PD-L1 (CPS ≥1).
These results highlight the potential of KEYTRUDA in extending survival for certain patients with HER2-positive and PD-L1 positive gastric and gastroesophageal cancers. In the U.S., KEYTRUDA, combined with trastuzumab and chemotherapy, is approved for the first-line treatment of adults with HER2-positive gastric or GEJ adenocarcinoma whose tumours express PD-L1 (CPS ≥1), based on tumour response rate and durability of response.
Continued approval of this indication may depend on further confirmation of clinical benefit. Since the FDA’s accelerated approval, the trial has met its primary endpoints of progression-free survival (PFS) and OS.
In August 2023, the European Commission approved KEYTRUDA for the same indication in adults with PD-L1 (CPS ≥1) expressing tumours based on the PFS results from KEYNOTE-811.
Merck continues to expand its clinical development programme for KEYTRUDA, exploring its use in various gastrointestinal cancers, including gastric, hepatobiliary, esophageal, pancreatic, and colorectal cancers.
Source: merck.com
