Coming up Short: Nivolumab + Chemotherapy Fails to Meet Primary Endpoint in Postoperative Adjuvant Setting for Stage III G/GEJ Cancer

Nivolumab + Chemotherapy for G/GEJ Cancer

Approximately 138,000 new cases of gastric cancer are diagnosed annually in Japan, contributing to a global total of about 1,089,000 cases. This disease leads to approximately 46,000 deaths each year in Japan, with a worldwide toll of around 769,000 deaths. Gastric cancer is the second most prevalent cancer in Japan, following lung cancer. Despite surgical resection, patients with pStage III gastric cancer face notably elevated recurrence rates, emphasizing the necessity for a novel treatment option for individuals affected by this disease.

The combination of nivolumab with chemotherapy as a first-line treatment, as well as nivolumab used as a monotherapy in the third-line or subsequent lines, has demonstrated survival advantages in patients diagnosed with unresectable advanced or recurrent gastric or gastroesophageal junction (G/GEJ) cancer. In Asia, adjuvant chemotherapy following D2 or more extensive gastrectomy is commonly employed as the standard of care for patients with pStage III G/GEJ cancer. However, conventional adjuvant chemotherapy has shown limited effectiveness in treating pStage III G/GEJ cancer.

ATTRACTION-5 is the first Phase III study to evaluate an immune checkpoint inhibitor in combination with adjuvant chemotherapy for pStage III G/GEJ cancer. It is a multicenter, randomized, double-blind study, conducted in Japan, South Korea, Taiwan, and China, evaluating OPDIVO in combination with chemotherapy (tegafur-gimeracil-oteracil potassium: S-1 monotherapy therapy up to 1 year, or capecitabine + oxaliplatin: CapeOX therapy up to 6 months), in patients with pStage III gastric cancer and esophagogastric junction cancer after curative resection undergoing postoperative adjuvant chemotherapy, versus placebo in combination with S-1 monotherapy or CapeOX therapy. In this study, patients received either OPDIVO 360 mg or a placebo every 3 weeks up to 1 year, in combination with chemotherapy. The primary endpoint of the study was relapse-free survival (RFS) as assessed by the Independent Radiologic Review Committee (IRRC). The secondary endpoints were RFS as assessed by the investigators and overall survival (OS).

Ono Pharmaceutical reported the first confirmatory results of Nivolumab plus chemotherapy as a postoperative adjuvant treatment for pathological Stage III G/GEJ Cancer at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. 

A total of 755 patients underwent randomization from February 2017 to August 2019: 377 were assigned to the nivolumab plus chemotherapy arm and 378 to the placebo plus chemotherapy arm. The final analysis of RFS was performed based on the clinical data cutoff of August 2022, with a minimum follow-up of 36 months after the last patient was randomized. The primary efficacy endpoint of centrally-assessed RFS was not met, with the 3-year RFS rates of 68.4% in the nivolumab plus chemotherapy arm and 65.3% in the placebo plus chemotherapy arm. The 3-year OS rates were 81.5% in the nivolumab plus chemotherapy arm and 78% in the placebo plus chemotherapy arm. 


Nivolumab + Chemotherapy

(N = 377)

Placebo + Chemotherapy

(N = 378)

3-year RFS rate (%)1



3-year RFS rate (%)2



3-year OS rate (%)



Note: 1 RFS per BICR; 2 RFS per investigator

KOL insights

“First major GI trial results from ASCO23. ATTRACTION-5 shows a lack of efficacy in adding Nivolumab to adjuvant chemo after at least D2 resection. Well done trial on 1st glance with OS data presented. Negative trials as important as positive.” –Expert Opinion.

“ATTRACTION-5 study showing adjuvant nivolumab + chemo didn't improve RFS vs. Adjuvant chemo in resectable gastric cancer. Maybe positive signal in PD-L1+ and stage IIIC pts? Overall a negative study.”- Expert Opinion.

Perhaps tumor presence is important for efficacy of perioperative IO  resectable gastric/GEJ cancer? Adjuvant nivolumab (ATTRACTION-5) negative for RFS but peri-operative toripalimab positive with higher tumor regression scores”- Expert Opinion.


The ATTRACTION-5 study of nivolumab plus chemotherapy vs. placebo plus chemotherapy 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. Standard adjuvant chemotherapy has shown limited efficacy for pStage III G/GEJ cancer, highlighting a need for a new treatment option in patients with this disease.

Get a more detailed overview of the key developments in the domain at: Gastric Cancer Market, Gastroesophageal Junction Adenocarcinoma Market, Gastric Cancer Pipeline Insight