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Nivolumab Demonstrates Significant Overall Survival Benefits in Patients with Previously Treated Esophageal Squamous-Cell Carcinoma Compared with Chemotherapy

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Esophageal squamous-cell carcinoma (ESCC) is the sixth leading cause of cancer-related mortality worldwide and, despite treatment, has a very low survival rate.1 Typically, it arises in the mid-portion of the esophagus from abnormal polyps and abnormal epithelium.1 Diets low in fruits and vegetables, smoking, and alcohol intake have been associated with the development of ESCC in the United States.1 In developing countries, high-temperature beverages and poor nutrition may also factor into the development of ESCC.1 Higher-risk regions include Central Asian countries, northern China, northern Iran, and southern Russia.1 In these areas, esophageal cancer is the fourth most common cancer cause and squamous-cell carcinoma comprises 90% of these cases.1

The phase 3 ATTRACTION-3 clinical trial demonstrated that nivolumab conveyed a significant improvement in overall survival (OS) with a tolerable safety profile compared with chemotherapy (paclitaxel or docetaxel) in previously treated unresectable, advanced or recurrent ESCC. In this study, 419 patients with unresectable advanced or recurrent ESCC that was refractory or intolerant to fluoropyrimidine or platinum-based chemotherapy were randomized into 2 study cohorts. Cohort 1 was treated with nivolumab, and cohort 2 was treated with the investigator’s choice of either paclitaxel or docetaxel chemotherapy. Patients were treated until their disease progressed or toxicity became intolerable. The study’s primary end point was OS. Also evaluated was the best overall response and treatment-related adverse event onset in the cohort treated with nivolumab. Researchers analyzed the 3-year survival rate of patients with ESCC using data from the study.

The median OS was 10.91 months for cohort 1 and 8.51 months for cohort 2 (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.64-0.97). At 24 months, the OS rate was 20.2% in cohort 1 and 13.5% in cohort 2. At 36 months, OS was 15.3% in cohort 1 and 8.7% in cohort 2. The evaluation of best overall response found median OS in the complete-response patients was 19.91 months and 15.41 months for those patients experiencing a partial response (HR, 0.84; 95% CI, 0.46-1.54). In patients with stable disease treated with nivolumab, the median OS was 17.38 months; in the chemotherapy-stable disease group, the median OS was 9.36 months (HR, 0.45; 95% CI, 0.26-0.78). No new treatment-related safety issues were found at the 3-year follow-up.

In patients with advanced ESCC, nivolumab demonstrated an increase in OS compared with patients treated with chemotherapy.


Chin K, Kato K, Byoung C, et al. Three-year follow-up of ATTRACTION-3: a phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy. J Clin Oncol. 2021;39(suppl_3):S204.


1. Recio-Boiles A, Babiker HM. Esophageal cancer. Updated July 21, 2021. In: StatPearls [Internet]. Accessed December 6, 2021.

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