FDA Approves Keytruda in HER2+ Gastric, Gastroesophageal Junction Cancer

The FDA has approved Keytruda plus chemotherapy in HER2+ gastric or GEJ adenocarcinoma with PD-L1–positive expression.

The U.S. Food and Drug Administration (FDA) has granted traditional approval to treatment with Keytruda (pembrolizumab) plus Herceptin (trastuzumab) and fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced, unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (combined positive score [CPS] of 1 or more).

According to an announcement from the regulatory agency on their official website, fda.gov, this approval based on the KEYNOTE-811 study, which evaluated the efficacy of Keytruda in combination with Herceptin and chemotherapy. The study enrolled 698 patients with HER2-positive advanced gastric or GEJ adenocarcinoma, none of whom had been previously treated with systemic therapy for metastatic disease. Of the 698 patients, 594 (85%) had tumors expressing PD-L1 with a CPS of 1 or more.

Moreover, Keytruda received accelerated approval status from the regulatory agency for this patient population on May 5, 2021, based on an interim analysis of the KEYNOTE-811 trial.

In patients with tumors that had PD-L1 CPS greater than or equal to 1, the median progression-free survival was 10.9 months in the Keytruda arm and 7.3 months in the placebo arm. The median overall survival was 20.1 months and 15.7 months in these respective arms. The overall response rate was 73% and 58%, while median duration of response was 11.3 months and 9.6 months.

The side effect profile for Keytruda was consistent with its known safety profile.

The recommended dose for Keytruda is 200 milligrams (mg) every three weeks or 400 mg every six weeks, in combination with Herceptin and chemotherapy.

More Information on the Combination Designation

Adenocarcinoma is cancer that forms in glandular tissue, which lines certain internal organs and produces substances like mucus, digestive juices, and other fluids. Most cancers of the breast, lung, esophagus, stomach, colon, rectum, pancreas, prostate and uterus are adenocarcinomas, according to the National Cancer Institute website, cancer.gov. Specifically, adenocarcinoma in the GEJ is cancer that forms in the glandular tissue where the stomach and esophagus meet.

As per cancer.gov, PD-L1 is a protein that helps regulate immune responses by acting as a "brake." It can be found on some normal cells and at higher levels on certain cancer cells. When PD-L1 binds to PD-1, a protein on T cells, it prevents T cells from attacking the cells, including cancer cells. Immune checkpoint inhibitors block this binding, allowing T cells to target and destroy cancer cells.

To further expand on the combination prior to its approval, investigators presented data from KEYNOTE-811 at the 2023 ESMO Congress wherein they examined the effects of the immunotherapy drug compared with a placebo in patients. The findings showed that patients receiving pembrolizumab had a longer period before their cancer worsened — 10 months on average compared with 8.1 months for those on placebo, according to information presented and simultaneously published in The Lancet.

For patients whose tumors expressed PD-L1 with a CPS of at least 1, Keytruda extended this period even further, with a median of 10.8 months versus 7.2 months in the placebo group.

In a later analysis, with more follow-up time, the results remained consistent, confirming Keytruda’s ability to slow disease progression.

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