Se Hoon Park1, Do Hoon Lim2, Tae Sung Sohn3, Jeeyun Lee1, Dae Young Zang4, Seung Tae Kim1, Jung Hoon Kang5, Sung Yong Oh6, In Gyu Hwang7, Jun Ho Ji8, Dong Bok Shin9, Jeong Il Yu2, Kyoung-Mee Kim10, Ji Yeong An3, Min Gew Choi3, Jun Ho Lee3, Sung Kim3, Jung Yong Hong1, Joon Oh Park1, Young Suk Park1, Ho Yeong Lim1, Jae Moon Bae11, Won Ki Kang12. 1. Division of Hematology-Oncology, Departments of Medicine. 2. Radiation Oncology. 3. Surgery. 4. Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeonggi-do, Korea. 5. Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea. 6. Department of Hematology-Oncology, Dong-A University, Busan, Korea. 7. Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea. 8. Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea. 9. Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea. 10. Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 11. Surgery. Electronic address: jmoon.bae@samsung.com. 12. Division of Hematology-Oncology, Departments of Medicine. Electronic address: wkkang@skku.edu.
Abstract
BACKGROUND:Adjuvant chemotherapy and/orchemoradiotherapy 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 gastric cancer. 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 one year, S-1 (2-weeks-on/1-week-off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for six months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according 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 to 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 vs. SOX, 0.692 (P=0.042) and S-1 vs. 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. CONCLUSION: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX, or SOX/RT was effective in prolonging DFS, when compared to S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2-gastrectomy.
RCT Entities:
BACKGROUND: Adjuvant chemotherapy and/or 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 gastric cancer. 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 one year, S-1 (2-weeks-on/1-week-off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for six months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according 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 to 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 vs. SOX, 0.692 (P=0.042) and S-1 vs. 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. CONCLUSION: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX, or SOX/RT was effective in prolonging DFS, when compared to S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2-gastrectomy.