As reported in The Lancet Oncology by Kato et al, the phase III ATTRACTION-3 trial conducted in predominantly Asian patients has shown a survival benefit with nivolumab vs paclitaxel or docetaxel in patients with advanced esophageal squamous cell carcinoma who were refractory to or intolerant of prior fluoropyrimidine-based and platinum-based chemotherapy.  

Study Details

The open-label trial included 419 patients from 90 sites in eight countries. Overall, 96% of patients in each group were Asian.

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Patients were randomly assigned between January 2016 and May 2017 to receive nivolumab at 240 mg every 2 weeks (n = 210), or investigator’s choice of paclitaxel at 100 mg/m² once per week for 6 weeks then 1 week off or docetaxel at 75 mg/m² every 3 weeks (n = 209). Treatment continued until investigator-assessed disease progression on Response Evaluation Criteria in Solid Tumors, version 1.1, or unacceptable toxicity. 

The primary endpoint was overall survival in the intention-to-treat population.

Survival Results

Median follow-up for overall survival was 10.5 months in the nivolumab group and 8.0 months in the chemotherapy group. Median overall survival was 10.9 months in the nivolumab group vs 8.4 months in the chemotherapy group (hazard ratio [HR] = 0.77, P = .019). Survival was 47% vs 34% at 12 months and 31% vs 21% at 18 months. Median progression-free survival was 1.7 vs 3.4 months (HR = 1.08, 95% confidence interval = 0.87–1.34).

Among 171 patients in the nivolumab group and 158 in the chemotherapy group with baseline measurement of target lesions, objective response was observed in 19% vs 22%. The median duration of response was 6.9 vs 3.9 months.

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 18% of the nivolumab group and 63% of the chemotherapy group. The most common event in the nivolumab group was anemia (2%); the most common events in the chemotherapy group were decreased neutrophil count (28%) and decreased white blood cell count (22%). Treatment-related serious adverse events occurred in 16% vs 23% of patients; the most common in the nivolumab group were pyrexia (2%) and interstitial lung disease (2%), and the most common in the chemotherapy group were febrile neutropenia (8%) and decreased appetite (3%).

Treatment-related adverse events led to discontinuation of treatment in 9% of patients in each group. Two deaths in the nivolumab group (due to interstitial lung disease and pneumonitis, respectively) and three in the chemotherapy group (due to pneumonia, spinal cord abscess, and interstitial lung disease, respectively) were considered related to treatment.

The investigators concluded, “Nivolumab was associated with a significant improvement in overall survival and a favorable safety profile compared with chemotherapy in previously treated patients with advanced esophageal squamous cell carcinoma, and might represent a new standard second-line treatment option for these patients.”

Ken Kato, MD, of the Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by ONO Pharmaceutical and Bristol-Myers Squibb. For full disclosures of the study authors, visit thelancet.com.