9/4/2023 0 Comments Keynote 590![]() The study randomly assigned patients to pembrolizumab monotherapy (n=256), pembrolizumab plus chemotherapy (cisplatin+5-FU n=257), or placebo plus chemotherapy (n=250) in a complex statistical design that had important ramifications for the final results. 6 The study examined the efficacy of pembrolizumab in the first-line treatment of metastatic programmed death ligand 1 (PD-L1)–positive GC or GEJ adenocarcinoma (Table 1). Given the signal of benefit for adding pembrolizumab (Keytruda, Merck) to chemotherapy in the phase 2 KEYNOTE-059 study, 5 KEYNOTE-062 investigated the addition of pembrolizumab further in a phase 3 design. Until recently, first-line treatment for advanced or metastatic gastroesophageal adenocarcinoma had been a platinum/fluoropyrimidine doublet, most commonly oxaliplatin combined with capecitabine (CAPOX) or 5-fluorouracil (5-FU FOLFOX). This review highlights some of the recently presented data and reviews the landscape of treatment in patients with gastroesophageal adenocarcinoma. 4 Over the past year, multiple studies have been presented and subsequently changed the standard of care for patients with both HER2-amplified and HER2-negative gastroesophageal adenocarcinoma. 3 However, the median overall survival (mOS) of patients with gastroesophageal adenocarcinoma is less than a year, except for the 15% to 20% of patients with human epidermal growth factor receptor 2 (HER2) overexpression, in whom median survival is improved by the addition of trastuzumab to the chemotherapy combination. ![]() The standard of care for unresectable locally advanced or metastatic gastroesophageal adenocarcinoma has long been systemic chemotherapy, which improves survival and quality of life. EC can be squamous cell carcinoma or adenocarcinoma. GC and GEJ cancer are typically adenocarcinomas. ![]() In addition, they may be classified as gastric cancer (GC), esophageal cancer (EC), and gastroesophageal junction (GEJ) cancer. 2 Gastroesophageal cancers can be divided into adenocarcinomas and squamous cell carcinomas. 1 Although less common in the United States than in Asia, gastroesophageal cancers accounted for more than 26,000 deaths in the United States in 2021. Gastroesophageal cancers are an important cause of morbidity and mortality worldwide. Chemoimmunotherapy combinations are now considered the standard of care for a significant number of patients with gastroesophageal adenocarcinomas. Furthermore, a phase 2 study revealed that trastuzumab deruxtecan, a new antibody-drug conjugate, significantly improved survival in comparison with chemotherapy among patients with HER2-positive gastric cancer in the refractory setting, and it produced a signal of efficacy in the second-line setting. Similarly, in patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive gastroesophageal adenocarcinoma, the addition of pembrolizumab to chemotherapy and trastuzumab has significantly improved efficacy. The addition of nivolumab to first-line chemotherapy has led to survival benefit in patients who have metastatic gastroesophageal adenocarcinoma with a programmed death ligand 1 combined positive score of 5 or greater. Abstract: The treatment landscape for gastroesophageal adenocarcinomas has significantly changed over the last year.
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