Neoadjuvant doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy plus radiotherapy for locally advanced OSCC

Neoadjuvant therapy is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma (LA OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. The phase 3 JCOG1109 NExT trial, at 44 centers in Japan compared neoadjuvant doublet chemotherapy (NeoCF), neoadjuvant triple chemotherapy (NeoCF+D), and neoadjuvant doublet chemotherapy plus radiotherapy (NeoCF+RT) followed by esophagectomy for LA OSCC in patients with ECOG PS 0 or 1. Primary endpoint was overall survival. Three-year OS was 72.1% with NeoCF+D, 68.3% with NeoCF+RT, and 62.6% with NeoCF; NeoCF+D was superior to NeoCF (HR 0.68; p=0.006), but NeoCF+RT was not (HR 0.84; p=0.12). Treatment-related adverse events leading to discontinuation of neoadjuvant therapy occurred in 9% of patients with NeoCF+D, 6% of patients with NeoCF+RT, and 4% of patients with NeoCF; while treatment-related deaths during neoadjuvant therapy occurred in 2%, 1%, and 2%, respectively. The authors conclude that neoadjuvant triplet chemotherapy followed by esophagectomy might be the new standard of care for LA OSCC in patients who are in good condition.