The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of pembrolizumab plus trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the frontline treatment of patients with advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma whose tumors have a PD-L1 combined positive score of at least 1.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of pembrolizumab (Keytruda) plus trastuzumab (Herceptin), fluoropyrimidine- and platinum-containing chemotherapy for the frontline treatment of patients with advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors have a PD-L1 combined positive score (CPS) of at least 1.1
The recommendation is based on interim data from the phase 3 KEYNOTE-811 trial (NCT03615326), which demonstrated a statistically significant improvement in progression-free survival (PFS) and objective response rate (ORR) with pembrolizumab plus trastuzumab and chemotherapy vs trastuzumab and chemotherapy alone in patients with PD-L1–positive tumors––this population represented more than 80% of patients in the study.2
These PFS results will be presented at an upcoming medical conference.
The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union (EU), and a final decision is expected in the third quarter of 2023. Approval of the regimen would render pembrolizumab the first immunotherapy to be indicated for the treatment of patients with newly diagnosed HER2-positive advanced gastric/GEJ cancer and positive PD-L1 expression in the European Union.
“This positive CHMP opinion reinforces our commitment to bringing meaningful treatment options to patients living with HER2-positive gastric or GEJ cancer, whose tumors express PD-L1 with a CPS of [at least] 1, in the EU,” Scot Ebbinghaus, MD, vice president, global clinical development, Merck Research Laboratories, stated in a news release. “We look forward to the European Commission’s decision and are excited at the possibility of bringing the first approved immunotherapy regimen for the first-line treatment of these patients with HER2-positive advanced gastric or GEJ cancer to the EU.”
In May 2021, the FDA granted accelerated approval to pembrolizumab plus trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma.3
The approval was based on earlier data from KEYNOTE-811, in which the ORR was 74% (95% CI, 66%-82%) with the pembrolizumab regimen vs 52% (95% CI, 43%-61%) with trastuzumab and chemotherapy alone (1-sided P < .0001).4
The double-blind, global, phase 3 study enrolled previously untreated patients with HER2-positive advanced gastric/GEJ adenocarcinoma. Patients were randomly assigned to receive pembrolizumab at 200 mg every 3 weeks or placebo plus trastuzumab at 6 mg/kg every 3 weeks following an 8-mg/kg loading dose and 5-fluorouracil at 800 mg/m2 on days 1 to 5 every 3 weeks plus cisplatin at 80 mg/m2 every 3 weeks or capecitabine at 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks plus oxaliplatin at 130 mg/m2 every 3 weeks.
The co-primary end points of the trial were overall survival (OS) and PFS per RECIST v1.1 criteria, as assessed by blinded independent central review (BICR). At the time of accelerated approval, a trend toward improved OS with the pembrolizumab regimen was noted in the intention-to-treat population, but this difference was not statistically significant.2 Secondary end points included ORR and duration of response by RECIST v1.1 criteria and BICR, as well as safety.
Notably, Merck is working with the FDA to update this indication to patients whose tumors are PD-L1 positive.