FDA Fully Approves Pembrolizumab/Trastuzumab Regimen in HER2+ Gastric Cancer

Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, discusses the standard approval of pembrolizumab (Keytruda) plus trastuzumab (Herceptin) and chemotherapy for the treatment of patients with HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, based on the final KEYNOTE-811 trial (NCT03615326) data.¹

On March 19, 2025, the FDA granted standard approval to pembrolizumab with trastuzumab and chemotherapy in this patient population. However, the FDA previously granted accelerated approval to the combination for the first-line treatment of patients with locally advanced, unresectable, or metastatic HER2-positive gastric or GEJ adenocarcinoma in May 2021, based on overall response rate (ORR) data from the first interim analysis of KEYNOTE-811.²

“Pembrolizumab in combination with trastuzumab and chemotherapy has been a practice-changing treatment for HER2-positive disease. In fact, even as far back as 2019, when we initially were accruing to the phase 3 study in the United States, we had trouble randomizing patients to the non-pembrolizumab-containing arm because many…were aware of our initial phase 2 data that we published in Lancet Oncology, and they did not want to be randomized to the non-pembrolizumab-containing arm,” explains Janjigian.

“We did finish the accrual to KEYNOTE-811 and of course, the final overall survival data was published and presented…showing median overall survival of 20 months in this population, compared with a median overall survival of less than 15 months based on the ToGA study [NCT01041404],” she continues.

In this video, Janjigian further discusses how she sees this standard approval impacting treatment algorithms in community oncology settings, especially compared with the prior accelerated approval.

REFERENCES:

1. FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1). News release. FDA. March 19, 2025. Accessed March 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma

2. FDA grants accelerated approval to pembrolizumab for HER2-positive gastric cancer. News release. FDA. May 5, 2021. Accessed March 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-her2-positive-gastric-cancer