FDA Restricts Use of Immunotherapies in Gastric, Esophageal Cancers

 The FDA narrowed the indications for pembrolizumab (Keytruda)

opens in a new tab or window and nivolumab (Opdivo)opens in a new tab or window in gastric, gastroesophageal junction (GEJ), and esophageal cancers, according to letters sent to the respective drugmakers.

The agency had originally granted PD-L1 agnostic approval for the two immune checkpoint inhibitors as first-line treatment for advanced gastroesophageal cancers.

However, based on phase III trial data that became available since those initial approvals, the FDA's Oncologic Drugs Advisory Committee last year votedopens in a new tab or window that PD-1 inhibitors do not have a favorable risk/benefit profile in gastric/gastroesophageal junction (GEJ), and esophageal cancers with PD-L1 expression <1.

Now, nivolumab -- in combination with chemotherapy -- is indicated for the first-line treatment of adults with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC), and the treatment of adults with advanced or metastatic gastric cancer, GEJ, and esophageal adenocarcinoma whose tumors express PD-L1 ≥1.

In addition, approval for nivolumab plus ipilimumab (Yervoy) as first-line treatment of unresectable advanced or metastatic ESCC has been restricted to those with PD-L1 expression ≥1.

The change for pembrolizumab applies to two indications:

• The PD-1 inhibitor is now indicated in combination with chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors express PD-L1 ≥1.
• And pembrolizumab is now also indicated for patients with locally advanced or metastatic esophageal or GEJ adenocarcinoma that is not amenable to surgical resection or definitive chemoradiation in combination with chemotherapy for patients with tumors that express PD-L1 ≥1. (The checkpoint inhibitor is also approved for these patients as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 ≥10.)

In March, the FDA also granted full approvalopens in a new tab or window to pembrolizumab with trastuzumab (Herceptin) and chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma, but that was already for the PD-L1-positive subset.

https://www.medpagetoday.com/hematologyoncology/othercancers/116000