作者
Masanori Terashima,Yoon‐Koo Kang,Young Woo Kim,Narikazu Boku,Hyun Cheol Chung,Jen‐Shi Chen,Jiafu Ji,Ta‐Sen Yeh,Li Tzong Chen,Min‐Hee Ryu,Jong Gwang Kim,Takeshi Omori,Sun Young Rha,Tae Yong Kim,Keun Won Ryu,Shinichi Sakuramoto,Yasunori Nishida,Noriyoshi Fukushima,Takanobu Yamada,Mitsuru Sasako
摘要
4000 Background: Nivolumab plus chemotherapy (N+C) in the first-line treatment and nivolumab monotherapy in the third- or later-line have shown survival benefit in patients with unresectable advanced or recurrent G/GEJ cancer. Adjuvant chemotherapy after D2 or more extended gastrectomy is a widely used standard of care for pStage III G/GEJ cancer in Asia. However, standard adjuvant chemotherapy has shown limited efficacy for pStage III G/GEJ cancer. ATTRACTION-5 is the first phase 3 study to evaluate an immune checkpoint inhibitor in combination with adjuvant chemotherapy for pStage III G/GEJ cancer. Here, we report the first confirmatory results of N+C as postoperative adjuvant treatment. Methods: The ATTRACTION-5 study is a multicenter, double-blind, randomized study conducted in Japan, Korea, Taiwan, and China. We enrolled patients with pStage III G/GEJ cancer who had undergone D2 or more extended gastrectomy. Investigators selected an appropriate adjuvant chemotherapy (tegafur/gimeracil/oteracil [S-1] therapy or capecitabine plus oxaliplatin [CapeOX] therapy) for each patient, and thereafter patients were randomly assigned (1:1) to the N+C or placebo plus chemotherapy (P+C) arm, using the allocation factors of country and disease stage. The primary endpoint was centrally-assessed relapse-free survival (RFS). The sample size was calculated, based on the results of the ACTS-GC study and the CLASSIC study (The assumed hazard ratio [HR], 0.67; the assumed 3-year RFS, 71% vs 60%). Secondary endpoints were investigator-assessed RFS, overall survival (OS), and 3-year RFS and OS rates. Results: A total of 755 patients underwent randomization from February 2017 to August 2019: 377 were assigned to the N+C arm and 378 to the P+C arm. The final analysis of RFS was performed based on the clinical data cutoff of August 2022, with the minimum follow-up of 36 months after the last patient was randomized. The primary efficacy endpoint of centrally-assessed RFS was not met (HR, 0.90; 95.72% CI, 0.69–1.18; P=0.4363), with the 3-year RFS rates of 68.4% (95% CI, 63.0–73.2) in the N+C arm and 65.3% (95% CI, 59.9–70.2) in the P+C arm. The completion rate of the planned postoperative adjuvant treatment was 61.5% in the N+C arm and 71.4% in the P+C arm. Incidences of grade≥3 TRAEs, serious TRAEs, and TRAEs leading to discontinuation were 54.4%, 25.3%, and 9.2%, respectively, in the N+C arm and 46.8%, 10.7%, and 3.5% in the P+C arm. Conclusions: The ATTRACTION-5 study of N+C vs P+C in patients with pStage III G/GEJ cancer after D2 or more extended gastrectomy did not meet the primary endpoint of RFS. The safety profile in the ATTRACTION-5 study was consistent with its known safety profile. Clinical trial information: NCT03006705 .