On 5 May 2021, the US Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda, Merck & Co.) in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2 positive gastric or gastro-oesophageal junction (GEJ) adenocarcinoma.<\/p>\n
Approval was based on the prespecified interim analysis of the first 264 patients of the ongoing KEYNOTE-811 (NCT03615326), a multicentre, randomised, double\u2011blind, placebo\u2011controlled study in patients with HER2\u2011positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease. Patients were randomised (1:1) to receive pembrolizumab 200 mg or placebo every 3 weeks, in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.<\/p>\n
The main efficacy measure for this analysis was overall response rate (ORR) assessed by blinded independent review committee. The ORR was 74% (95% confidence interval [CI] 66, 82) in the pembrolizumab arm and 52% (95% CI 43, 61) in the placebo arm (one-sided p-value < 0.0001, statistically significant).<\/p>\n
The median duration of response was 10.6 months (range 1.1+, 16.5+) for patients treated with pembrolizumab and 9.5 months (range 1.4+, 15.4+) for those in the placebo arm.<\/p>\n
The adverse reaction profile observed in patients receiving pembrolizumab in KEYNOTE-811 study is consistent with the known pembrolizumab safety profile.<\/p>\n
The recommended pembrolizumab dose for adult patients with locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma in combination with trastuzumab and chemotherapy is 200 mg every 3 weeks or 400 mg every 6 weeks.<\/p>\n
Full prescribing information for Keytruda is available here<\/a>.<\/p>\n This review used the Real-Time Oncology Review pilot programme, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment.<\/p>\n This application was granted priority review.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n