News Report · Oncology

FDA Approves Pembrolizumab for HER2-Positive Gastric Cancer: 10.9 Months PFS in KEYNOTE-811 Trial

June 09, 2026

Clinical Perspective

The approval of pembrolizumab in combination with trastuzumab and chemotherapy provides a significant treatment option for patients with HER2-positive gastric cancer, particularly those with PD-L1 expression.

Dr. Meera Pillai · Oncology

Pembrolizumab (Keytruda) reduced progression-free survival (PFS) by 10.9 months versus chemotherapy in patients with locally advanced unresectable HER2-positive gastric or gastroesophageal junction adenocarcinoma in the KEYNOTE-811 trial (HR 0.72; 95% CI 0.60-0.87) ^[1].

Clinical Context

Gastric cancer is a leading cause of cancer-related mortality worldwide, with a significant proportion of cases being diagnosed at an advanced stage. The current standard treatment for locally advanced unresectable gastric or gastroesophageal junction adenocarcinoma typically involves chemotherapy, often in combination with targeted therapies. However, many patients experience disease progression despite initial treatment, highlighting a critical need for more effective therapeutic options. The KEYNOTE-811 trial evaluates the efficacy of pembrolizumab, an anti-PD-1 therapy, in combination with trastuzumab and chemotherapy for this patient population, particularly those with tumors expressing PD-L1 (CPS ≥1).

Key Findings

The KEYNOTE-811 trial showed pembrolizumab reduced PFS by 10.9 months versus chemotherapy (HR 0.72; 95% CI 0.60-0.87) ^[1].
The trial enrolled 698 patients with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma ^[1].
Event rates: 10.9 months in the pembrolizumab arm versus 7.3 months in the placebo arm ^[1].
The primary endpoint was progression-free survival (PFS) ^[1].
Overall survival (OS) data demonstrated a median OS of 20.1 months in the pembrolizumab group compared to 15.7 months in the placebo group (HR 0.79; 95% CI 0.66-0.95) ^[1].
Pembrolizumab is administered at a dose of 200 mg intravenously every 3 weeks or 400 mg every 6 weeks in combination with trastuzumab and chemotherapy ^[1].
Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Nausea reported with pembrolizumab — exact frequency not available in public source summary ^[1].
Diarrhea reported — exact frequency not available in public source summary ^[1].
Fatigue reported ^[1].
Hyperglycemia reported — advise patients to monitor blood glucose levels during treatment ^[1].
Immune-mediated reactions such as pneumonitis and colitis reported ^[1].
Complete adverse event profile available in the full prescribing information for pembrolizumab (Keytruda) ^[1].

What This Means for Clinical Practice

Oncologists treating patients with locally advanced unresectable HER2-positive gastric or gastroesophageal junction adenocarcinoma may consider pembrolizumab in combination with trastuzumab and chemotherapy based on the trial criteria. The data supports a median PFS of 10.9 months with this regimen. What additional biomarkers could further refine patient selection for this treatment?

Study Design

KEYNOTE-811 was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 698 patients with HER2-positive gastric or gastroesophageal junction adenocarcinoma who had not previously received systemic therapy for metastatic disease. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR). Patients were randomized (1:1) to receive pembrolizumab 200 mg or placebo in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin. Clinicians should consult current prescribing information for full dosing guidance. The follow-up duration was not specified in the sources. Key limitations include the trial's focus on a specific patient population and the potential for selection bias in the enrollment process.

FAQ

What is pembrolizumab (Keytruda) approved for?

Pembrolizumab is approved for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (CPS ≥1) based on the KEYNOTE-811 trial results.

How does pembrolizumab work?

Pembrolizumab is an anti-PD-1 monoclonal antibody that works by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby enhancing the immune response against cancer cells.

What is the recommended dose of pembrolizumab?

The recommended dose of pembrolizumab is 200 mg intravenously every 3 weeks or 400 mg every 6 weeks in combination with trastuzumab and chemotherapy. Clinicians should consult current prescribing information for full dosing guidance.

What are the most common side effects of pembrolizumab?

Common side effects of pembrolizumab include nausea, diarrhea, fatigue, hyperglycemia, and immune-mediated reactions such as pneumonitis and colitis.

How does pembrolizumab compare to chemotherapy in this indication?

Pembrolizumab in combination with chemotherapy demonstrated a median PFS of 10.9 months compared to 7.3 months with chemotherapy alone in the KEYNOTE-811 trial.

Who qualifies for pembrolizumab treatment?

Patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (CPS ≥1) qualify for pembrolizumab treatment based on the trial criteria.

References

FDA — FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1)

FDA Approves Pembrolizumab for HER2-Positive Gastric Cancer: 10.9 Months PFS in KEYNOTE-811 Trial

FDA Approves Pembrolizumab for HER2-Positive Gastric Cancer: 10.9 Months PFS in KEYNOTE-811 Trial

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

What This Means for Clinical Practice

Study Design

FAQ

References

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