#VisualAbstract: Pembrolizumab enhances progression-free survival in patients with HER2-positive gastro-esophageal cancer

1. Progression-free survival was significantly greater among patients in the pembrolizumab group compared to placebo (10.0 vs. 8.1 months).

2. 1% of patients in each group experienced treatment-related mortality.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Limited evidence exists on combined PD-1 and HER2 blockade with chemotherapy in HER2-positive gastro-esophageal cancer. This randomized controlled trial aimed to assess the safety and efficacy of adding pembrolizumab or placebo to the current standard-of-care (fluorouracil plus cisplatin or capecitabine plus oxaliplatin) among patients with HER2-positive gastric or gastro-esophageal cancer. The primary outcome was progression-free survival, while the key secondary outcome was overall survival. According to study results, pembrolizumab significantly improved progression-free survival compared to placebo, particularly in tumours with PD-L1 combined score above 1. Although well done, this study was limited by ongoing overall survival follow-up and the need for final analysis.

Click to read the study in The Lancet

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In-depth [randomized-controlled trial]: Between Oct 5, 2018, and Aug 6, 2021, 1327 patients were screened for eligibility across 168 medical centers in 20 countries. Included were patients ≥ 18 years with metastatic HER2-positive gastro-esophageal cancer, lacking prior treatment. Altogether, 698 patients (350 in pembrolizumab and 348 in placebo) were included in the final analysis. The primary outcome of progression-free survival significantly favoured pembrolizumab (10.0 vs. 8.1 months, hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.61–0.87, p=0.0002). The secondary outcome of overall survival showed improvement but did not meet the significance criteria (20.0 vs. 16.8 months, HR 0.84, 95% CI 0.70–1.01, p=0.084). Most adverse events were mild-to-moderate with 1% of patients in each group experiencing mortality. Findings from this study suggest that pembrolizumab, added to trastuzumab and chemotherapy, enhances progression-free survival in HER2-positive gastro-esophageal cancer.

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