KEYNOTE-061, Pembrolizumab does not meet primary endpoint of overall survival in previously treated patients with gastric or gastroesophageal junction adenocarcinoma
The pivotal phase 3 KEYNOTE-061 trial investigating Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, as a second-line treatment for patients with advanced gastric or gastroesophageal junction ( GEJ ) adenocarcinoma, did not meet its primary endpoint of overall survival ( OS ) ( hazard ratio, HR, 0.82 [ 95% CI, 0.66-1.03 ]; p=0.042 [ one-sided ] ) in patients whose tumors expressed PD-L1 [ Combined Positive Score ( CPS ) greater than or equal to 1 ].
Additionally, progression free survival ( PFS ) in the PD-L1 positive population did not show statistical significance.
The safety profile observed in KEYNOTE-061 was consistent with that observed in previously reported studies of Pembrolizumab; no new safety signals were identified.
In September 2017, the U.S. Food and Drug Administration ( FDA ) approved Keytruda as a third-line treatment for previously treated patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction cancer whose tumors express PD-L1 ( CPS greater than or equal to 1 ) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and Platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.
The current indication remains unchanged and Merck continues to evaluate Pembrolizumab for gastric or GEJ adenocarcinoma through KEYNOTE-062, a phase 3 clinical trial studying Pembrolizumab as a monotherapy or in combination with chemotherapy as first-line treatment for patients with PD-L1 positive advanced gastric or gastroesophageal junction cancer, and with KEYNOTE-585, a phase 3 trial studying Pembrolizumab in combination with chemotherapy in a neoadjuvant/adjuvant setting.
KEYNOTE-061 is a randomized, open-label, pivotal phase 3 study investigating Pembrolizumab as a monotherapy versus Paclitaxel in patients with advanced gastric or GEJ adenocarcinoma whose disease progressed after first-line treatment with Platinum and fluoropyrimidine doublet therapy.
The primary endpoints are PFS and OS in patients whose tumors express PD-L1 ( CPS more than 1 ); secondary endpoints include PFS, OS and overall response rate ( ORR ) in patients regardless of PD-L1 expression.
The study randomized 592 patients to receive Pembrolizumab ( 200 mg fixed dose every three weeks ) or Paclitaxel [ 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle ].
Gastric cancer is a type of cancer that begins in the stomach and tends to develop slowly over many years.
Most gastric cancers are adenocarcinomas, which develop from the cells of the innermost lining ( mucosa ) of the stomach.
Risk factors for gastric cancer include gender, age, ethnicity, geography and infection with Helicobacter pylori.
Worldwide, gastric cancer is the fifth most common type of cancer and the third leading cause of cancer death. Each year there are approximately 952,000 newly diagnosed cases of gastric cancer resulting in approximately 723,000 deaths worldwide.
It is estimated that in 2017, more than 10,000 people will die from gastric cancer in the U.S. alone.
Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. ( Xagena )
Source: Merck, 2017