Pembrolizumab is approved by the USFDA for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1)

On March 19, 2025, the Food and Drug Administration officially approved pembrolizumab (Keytruda, Merck) to be used along with trastuzumab and chemotherapy that includes fluoropyrimidine and platinum for the first treatment of adults with locally advanced, inoperable, or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma that shows PD-L1 expression (CPS ≥1).

Pembrolizumab was granted accelerated approval for this indication on May 5, 2021, based on an interim analysis of the trial detailed below.

Effectiveness and Safety

The effectiveness was tested in KEYNOTE-811 (NCT03615326), a big study with 698 patients who had HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma and had not been treated before for their metastatic disease. They took part in a randomized, double-blind trial that compared the treatment to a placebo. Out of these 698 patients, 594 (85%) had tumors that showed PD-L1 expression at a CPS ≥1, as checked by the PD-L1 IHC 22C3 pharmDx kit.

Of these 698 patients, 594 (85%) had tumors that showed PD-L1 expression at a CPS ≥1, as tested by the PD-L1 IHC 22C3 pharmDx kit. Of the 698 patients, 594 (85%) exhibited tumors with PD-L1 expression at a CPS ≥1, as determined by the PD-L1 IHC 22C3 pharmDx kit. Patients were randomly divided into equal groups to receive either pembrolizumab 200 mg or a placebo, along with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The main results looked at in patients were how long they lived without their disease getting worse (progression-free survival, or PFS) as checked by an independent review, and how long they lived overall (overall survival, or OS). The additional results included the overall response rate (ORR) and how long the response lasted (duration of response or DOR). The supplementary outcome measures comprised overall response rate (ORR) and duration of response (DOR).

People who received pembrolizumab along with trastuzumab and chemotherapy had a noticeable improvement in overall survival (OS) and progression-free survival (PFS) compared to those who got a placebo with trastuzumab and chemotherapy.

In patients with tumors exhibiting PDL1 CPS≥1, the median progression-free survival (PFS) was 10.9 months (95% CI: 8.5, 12.5) in the pembrolizumab group and 7.3 months (95% CI: 6.8, 8.4) in the placebo group (Hazard ratio [HR] 0.72 [95% CI: 0.60, 0.87]). The median overall survival (OS) was 20.1 months (95% confidence interval [CI]: 17.9, 22.9) and 15.7 months (95% CI: 13.5, 18.5) in the respective groups, with a hazard ratio (HR) of 0.79 (95% CI: 0.66, 0.95).

The overall response rate (ORR) was 73% (95% confidence interval: 68, 78) and 58% (95% confidence interval: 53, 64), whereas the median duration of response (DOR) was 11.3 months (95% confidence interval: 9.9, 13.7) and 9.6 months (95% confidence interval: 7.1, 11.2).

The adverse reaction profile reported in patients administered pembrolizumab aligned with the established safety profile of pembrolizumab.

The advised dosage of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks, administered alongside trastuzumab and chemotherapy.