Oxaliplatin in perioperative chemotherapy for gastric and gastroesophageal junction (GEJ) adenocarcinoma

ABSTRACT

Introduction: Platinum-based chemotherapy remains standard-of-care for gastric and gastroesophageal junction (GEJ) adenocarcinoma. For locally advanced resectable disease, perioperative treatment with cisplatin-based doublet or triplet chemotherapy regimens had been the predominant approach in Europe and the US, based on pivotal phase III trials including the MAGIC study. Results from more recent landmark studies including the German FLOT4 and the Asian CLASSIC trials have, however, triggered a shift from cisplatin towards oxaliplatin-based chemotherapy protocols in the perioperative setting.

Areas covered: This drug profile summarizes current state-of-the-art of perioperative and adjuvant treatment for locally advanced resectable gastric/GEJ cancers with a special focus on the increasingly predominant role of oxaliplatin over cisplatin in this setting. We review pharmacology, clinical efficacy, and safety profile of oxaliplatin and oxaliplatin combination regimens. We highlight recent advances and ongoing developments in the field.

Expert opinion: While the adoption of oxaliplatin-containing combination regimens for perioperative therapy of gastric/GEJ cancers represents a significant step ahead, many pivotal questions remain unanswered. At the sample time, the evolution of molecular subtyping and immunotherapy is likely to dramatically change clinical practice in the foreseeable future.

KEYWORDS:

• Perioperative chemotherapy
• gastric cancer
• gastroesophageal junction adenocarcinoma
• esophageal cancer
• oxaliplatin
• efficacy
• safety

Article highlights

• The perioperative treatment landscape for gastric/GEJ cancer is shifting from cisplatin- towards oxaliplatin-based combination chemotherapy.

• The landmark FLOT4 and CLASSIC phase III trials have shown superior PFS and OS for oxaliplatin combinations in the perioperative and adjuvant settings.

• For advanced irresectable and metastatic gastric/GEJ cancer, 5 published randomized trials show non-inferior efficacy and an overall more favorable safety profile for oxaliplatin over cisplatin combinations.

• Ongoing trials further evaluate the role of neoadjuvant chemoradiation and explore the addition of molecularly targeted agents and immune checkpoint inhibitors to the FLOT backbone aiming to personalize perioperative treatment.

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Declaration of interest

No potential conflict of interest was reported by the authors.