On November 7, 2023, the Food and Drug Administration (FDA) made significant updates to the existing indication of pembrolizumab (Keytruda, Merck) for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. These changes come as part of the FDA’s commitment to advancing cancer treatment options, bringing hope to patients and healthcare providers alike.
Target Patient Population
The revised indication now specifies the use of pembrolizumab in combination with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy. It is limited to patients whose tumors express PD-L1 (CPS ≥ 1), as determined by an FDA-approved test.
Companion Diagnostic Device Approval
The FDA also granted approval to the Agilent PD-L1 IHC 22C3 pharmDx as a companion diagnostic device. This device aids in selecting patients with gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥ 1), ensuring a more targeted and personalized approach to treatment.
Clinical Trial Insights
KEYNOTE-811 Trial
The efficacy of pembrolizumab was evaluated in the KEYNOTE-811 trial, a multicenter, randomized, double-blind study. Participants with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma, who had not previously received systemic therapy for metastatic disease, were enrolled.
Major Efficacy Outcomes
The primary efficacy outcomes included overall survival (OS) and progression-free survival (PFS). An interim analysis revealed a remarkable objective response rate (ORR) of 74% in the pembrolizumab plus chemotherapy arm, compared to 52% in the placebo plus chemotherapy arm (p-value <0.0001).
Safety Profile
The safety profile of pembrolizumab, when combined with trastuzumab and chemotherapy, was generally consistent with the known safety profiles of trastuzumab + chemotherapy or pembrolizumab monotherapy. This reassures healthcare providers and patients about the treatment’s safety.
Treatment Guidelines
1. Recommended Pembrolizumab Dose
Healthcare providers are advised to administer pembrolizumab at a dose of 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months. Pembrolizumab should be given prior to trastuzumab and chemotherapy when administered on the same day.
2. Approval Timeline
Notably, the FDA approved this application approximately 7 months ahead of the FDA goal date, highlighting the urgency and importance of this treatment option.
Reporting Adverse Events
Healthcare professionals play a crucial role in patient safety. Any serious adverse events suspected to be associated with the use of pembrolizumab and other medications should be reported to the FDA’s MedWatch Reporting System at medwatch.com or by calling 1-800-FDA-1088.
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About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.