A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.
BACKGROUND
Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC.


PATIENTS AND METHODS
The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146).


RESULTS
A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable.


CONCLUSIONS
In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.
['Park|S H|SH|', 'Lim|D H|DH|', 'Sohn|T S|TS|', 'Lee|J|J|', 'Zang|D Y|DY|', 'Kim|S T|ST|', 'Kang|J H|JH|', 'Oh|S Y|SY|', 'Hwang|I G|IG|', 'Ji|J H|JH|', 'Shin|D B|DB|', 'Yu|J I|JI|', 'Kim|K-M|KM|', 'An|J Y|JY|', 'Choi|M G|MG|', 'Lee|J H|JH|', 'Kim|S|S|', 'Hong|J Y|JY|', 'Park|J O|JO|', 'Park|Y S|YS|', 'Lim|H Y|HY|', 'Bae|J M|JM|', 'Kang|W K|WK|', '|||']
D000971:Antineoplastic Combined Chemotherapy Protocols D000069287:Capecitabine D017024:Chemotherapy, Adjuvant D018572:Disease-Free Survival D005472:Fluorouracil D006801:Humans D009364:Neoplasm Recurrence, Local D009367:Neoplasm Staging D000077150:Oxaliplatin D013274:Stomach Neoplasms
gastric cancer adjuvant chemotherapy radiotherapy