Stage II gastric cancer: 1 year of S-1 remains standard of care
Mené sur 590 patients atteints d'un cancer de l'estomac de stade II, cet essai de phase III évalue l'intérêt, du point de vue de la survie sans récidive et de la toxicité, de réduire la durée de référence d'un traitement adjuvant par S-1 (réduction de la durée de 1 an à 6 mois)
In The Lancet Gastroenterology & Hepatology, Takaki Yoshikawa and colleagues report an important randomised, phase 3, non-inferiority trial comparing four courses (6 months) with eight courses (12 months) of adjuvant S-1 in stage II resected gastric cancer. The trial was stopped at early interim analysis, as non-inferiority in relapse-free survival for the shorter duration therapy could not be shown, and a likely inferior outcome (hazard ratio [HR] 2·52, updated to 1·84) was seen. Although the absolute number of relapse events for four courses (n=17) versus eight courses of therapy (n=11) was small, the authors correctly argue that the risk of harm outweighed continuation of the trial. There is a clear rationale to assess a shorter duration of adjuvant therapy, given the better prognosis for stage II compared with stage III disease. The original trial of adjuvant S-1 indicated a higher relative benefit in stage II (HR 0·518) than in stage III disease (0·665–0·855). The benefit for S-1 was also greater in node-negative (0·317) than in node-positive patients (0·606–0·917). The alternative adjuvant regimen after gastrectomy, 6 months of postoperative capecitabine and oxaliplatin, also achieved the greatest relative survival benefit in stage II (0·54) compared with stage III disease (0·67–0·75). By contrast with adjuvant S-1, capecitabine and oxaliplatin had a greater benefit in node positive (0·57) than in node-negative patients (0·79). This observation led many investigators in Asia to prefer combination chemotherapy with capecitabine and oxaliplatin to S-1 as adjuvant therapy in node-positive patients with gastric cancer. Combination rather than single agent adjuvant chemotherapy for stage III disease is also supported by the reporting of superior relapse-free survival for the combination of docetaxel and S-1 compared with S-1 alone in the JACCRO GC-1 trial. Combination chemotherapy, either S-1 plus docetaxel for 12 months or capecitabine and oxaliplatin for 6 months, is now the standard of care for adjuvant treatment of stage III gastric cancer.