FDA OKs Upfront Pembro for Advanced HER2+ Gastric Cancer

Nick Mulcahy


May 06, 2021

This week, the US Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda) in combination with other agents for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.

Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and an HER2-targeted therapy. However, that was an accelerated approval based on response rates, and it may be rescinded if the FDA follows the advice of its Oncologic Drugs Advisory Committee, which voted on April 29 to recommend withdrawing this approval because of a lack of evidence for clinical efficacy.

The reasoning behind this move was that another checkpoint inhibitor, nivolumab (Opdivo), had recently gained a full approval on the basis of a phase 3 trial that showed improved overall survival when nivolumab plus chemotherapy was used as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.

Patients were randomly assigned (1:1) to receive either pembrolizumab 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).

The median duration of response was 10.6 months in the pembrolizumab arm of the trial and 9.5 months in the placebo arm.

The adverse reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, said the FDA in a statement.

The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.

The FDA's review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and the Assessment Aid, a voluntary submission that facilitates the FDA's assessment.

Nick Mulcahy is an award-winning senior journalist for Medscape. He previously freelanced for HealthDay and MedPageToday and had bylines in WashingtonPost.com, MSNBC, and Yahoo. Email: nmulcahy@medscape.net and on Twitter: @MulcahyNick.

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