FDA Approves Pembrolizumab for HER2+ Gastric Cancer

FDA

The FDA has approved pembrolizumab for use in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the frontline treatment of patients with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.¹

The regulatory decision was based on data from a prespecified interim analysis of the first 264 patients enrolled to the KEYNOTE-811 trial (NCT03615326), which showed that the pembrolizumab combination elicited an overall response rate (ORR) of 74% (95% CI, 66-82) vs 52% (95% CI, 43-61) with placebo (one-sided P <.0001). The median duration of response (DOR) was 10.6 months (range, 1.1+ to 16.5+) in the pembrolizumab arm vs 9.5 months (range, 1.4+ to 15.4+) in the placebo arm.

The multicenter, randomized, double‑blind, placebo‑controlled trial enrolled patients with HER2‑positive advanced gastric or GEJ adenocarcinoma who had not received prior systemic therapy for metastatic disease.

To be eligible for enrollment, patients needed to be at least 18 years of age, have previously untreated histologically or cytologically confirmed locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, HER2 positivity, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 6 months.²

Participants were randomized 1:1 to receive either pembrolizumab at 200 mg or placebo every 3 weeks, in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The primary end points of the trial were progression-free survival and overall survival. Key secondary end points included ORR and DOR per RECIST v1.1 criteria and blinded independent central review, as well as safety. Health-related quality of life serves as an exploratory end point of interest.

The safety profile observed in patients who received the immunotherapy in KEYNOTE-811 proved to be consistent with the known safety profile of the agent.

References

1. FDA grants accelerated approval to pembrolizumab for HER2-positive gastric cancer. News release. FDA. May 5, 2021. Accessed May 5, 2021. https://bit.ly/3b027iL
2. Chung HCC, Bang Y-J, Fuchs CS, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol. 2021;17(5):491-501. doi:10.2217/fon-2020-0737