Progression-Free Survival Improved in Patients with HER2-Negative Recurrent or Advanced Gastric or Gastroesophageal Junction Cancer Receiving Nivolumab plus Chemotherapy

Web Exclusives —November 16, 2021

Gastric or gastroesophageal junction cancer (GEJC) is the third leading cause of cancer-related mortality with a <10% 5-year survival rate for patients.1 Most cases are diagnosed in the advanced stage when treatment is generally ineffective.2 The incidence of gastric cancer varies geographically, with Central and South America, East Asia, and Eastern European countries having higher incidence rates.2 Males and American Indian/Alaska Natives, Asian/Pacific Islanders, and Hispanics are at increased risk for developing gastric cancer.2 Although Helicobacter pylori infection has been identified as a main cause for gastric cancer, the consumption of alcohol and certain foods, cigarette smoking, gastroesophageal reflux disease, exposure to chemicals, gastric ulcer disease, and obesity also contribute to the development of the disease.2 First-line treatment for advanced gastric cancer and GEJC is chemotherapy with a platinum agent plus fluoropyrimidine.1 Immunotherapy has also been investigated as a treatment option for patients with advanced gastric cancer or GEJC, including the PD-1 inhibitor nivolumab.3 By inhibiting PD-1 and its interaction with PD-L1, nivolumab conveys potent antitumor activity, enhances the action of the immune system, and delays the proliferation of tumor cells.3 The ATTRACTION-4 clinical trial, a multicenter, phase 2/3 study, evaluated the use of nivolumab plus chemotherapy versus chemotherapy alone as first-line therapy in 724 patients in patients with HER2-negative recurrent or advanced gastric cancer or GEJC. The study’s primary end points were progression-free survival (PFS) and overall survival (OS) with safety also being evaluated.

Nivolumab or placebo was administered every 3 weeks until the disease progressed, or unacceptable toxicity occurred. The chemotherapy regimen consisted of either S-1, an oral fluoropyrimidine-based drug, plus oxaliplatin or capecitabine plus oxaliplatin. Patient assessment was performed every 6 weeks until week 54 when the assessment changed to every 12 weeks. At the interim analysis, PFS for the nivolumab-treated group was 10.5 months while PFS for the chemotherapy-alone group was 8.3 months. The median follow-up period at this point was 11.6 months. The final analysis had a median follow-up of 26.6 months. OS at final analysis was 17.5 months for the nivolumab-treated group and 17.2 months for the chemotherapy-alone treatment group. The objective response rate was 57.5% for the nivolumab-treated group and 47.8% for the chemotherapy-alone treatment group. Grade ≥3-5 treatment-related adverse event rates were 57.9% in the nivolumab plus chemotherapy treatment group and 49.2% in the chemotherapy-alone treatment group.

Nivolumab plus chemotherapy improved PFS in patients with HER2-negative recurrent or advanced gastric cancer or GEJC.


Boku N, Ryu M, Oh D-Y, et al. Nivolumab plus chemotherapy versus chemotherapy alone in patients with previously untreated advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer: ATTRACTION-4 (ONO-4538-37) study. Ann Oncol. 2020;31(suppl_4):S1192.


  1. Selim JH, Shaheen S, Sheu WC, et al. Targeted and novel therapy in advanced gastric cancer. Exp Hematol Oncol. 2019;8:25.
  2. Wong MCS, Huang J, Chan PSF, et al. Global incidence and mortality of gastric cancer, 1980-2018. JAMA Netw Open. 2021;4:e2118457.
  3. Guo L, Zhang H, Chen B. Nivolumab as programmed death-1 (PD-1) inhibitor for targeted immunotherapy in tumor. J Cancer. 2017;8:410-416.
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Last modified: November 16, 2021

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