Nivolumab Demonstrates Significantly Superior Overall Survival Benefit Compared with Chemotherapy in Patients with Advanced Esophageal Cancer
Nivolumab Reduces the Risk of Death in Patients with Advanced Esophageal Cancer Compared to Chemotherapy23%，
Prolonged Median Overall Survival2.5month
On September 30, 2019, Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. announced the results of a Phase III clinical trial named ATTRACTION-3, which aimed to evaluate the efficacy and safety of nivolumab compared with chemotherapy (docetaxel or paclitaxel) in patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who were refractory or intolerant to prior fluoropyrimidine- and platinum-based combination therapy. Compared with chemotherapy, nivolumab demonstrated a statistically significant benefit in the primary endpoint of overall survival (OS), with a 23% reduction in the risk of death [HR 0.77; 95% CI: 0.62–0.96; p=0.019] and a 2.5-month improvement in median overall survival (mOS) [mOS was 10.9 months (95% CI: 9.2–13.3) for the nivolumab group versus 8.4 months (95% CI: 7.2–9.9) for the chemotherapy group]. The safety profile of nivolumab in this trial was consistent with that reported in previous clinical trials in esophageal squamous cell carcinoma and other solid tumors.
The study results were presented at the Presidential Symposium of the 2019 European Society for Medical Oncology (ESMO) Annual Meeting and simultaneously published in The Lancet Oncology.
The 12- and 18-month overall survival rates among patients treated with nivolumab were 47% (95% CI: 40–54) and 31% (95% CI: 24–37), respectively, compared with 34% (95% CI: 28–41) and 21% (95% CI: 15–27) in the chemotherapy group. Survival benefits with nivolumab were observed regardless of tumor PD-L1 expression levels. Furthermore, an exploratory analysis of patient-reported outcomes (PROs) demonstrated that nivolumab significantly improved patients’ quality of life compared with chemotherapy.
Professor, Yonsei University College of Medicine and Yonsei Cancer CenterByoung Chul ChoPh.D.stated, “The significant survival benefit, favorable safety profile, and patient-reported outcomes observed in this clinical study all indicate that nivolumab holds promise as an important new second-line treatment option for patients with advanced esophageal squamous cell carcinoma, offering the potential to prolong survival and improve quality of life.”
The objective response rates (ORR) were comparable between the nivolumab group and the chemotherapy group, at 19% (95% CI: 14–26) and 22% (95% CI: 15–29), respectively. However, the study demonstrated that nivolumab substantially prolonged the median duration of response (mDoR) to 6.9 months (95% CI: 5.4–11.1), compared with 3.9 months (95% CI: 2.8–4.2) in the chemotherapy group. At the data cutoff date, 7 patients in the nivolumab group maintained ongoing responses, versus 2 in the chemotherapy group. There was no significant difference in progression-free survival (PFS) between the nivolumab and chemotherapy groups, with a hazard ratio (HR) of 1.08 (95% CI: 0.87–1.34).
“These results are encouraging for patients with advanced esophageal squamous cell carcinoma, a condition that typically carries a poor prognosis. Importantly, nivolumab improved patient survival regardless of tumor PD-L1 expression levels.”Head of Gastrointestinal Oncology R&D, Bristol-Myers SquibbIan M. WaxmanDr.stated, “We are greatly encouraged by such significant progress in esophageal cancer research and look forward to expanding our studies on gastrointestinal tumors.”
Compared with chemotherapy, nivolumab was associated with fewer treatment-related adverse events (TRAEs). The overall incidence of TRAEs was 66% in patients receiving nivolumab versus 95% in those receiving chemotherapy. The incidence of grade 3–4 TRAEs was lower in the nivolumab group than in the chemotherapy group (18% vs. 63%), while the proportion of patients discontinuing treatment due to TRAEs was identical in both groups (9%).
AboutATTRACTION-3Research
ATTRACTION-3 is a multicenter, randomized, open-label, global Phase III clinical study designed to evaluate the efficacy and safety of nivolumab versus chemotherapy (docetaxel or paclitaxel) in patients with esophageal cancer who are refractory to or intolerant of prior fluoropyrimidine and platinum-based combination therapy. Patients enrolled in both groups were predominantly from Asia, accounting for 96% of the study population. Patients received treatment until disease progression or the occurrence of serious adverse events. The primary endpoint was overall survival (OS). Secondary endpoints included investigator-assessed objective response rate (ORR), progression-free survival (PFS), disease control rate, duration of response (DoR), and safety. The study was conducted by Ono Pharmaceutical Co., Ltd., which jointly developed nivolumab with Bristol-Myers Squibb Company.
About Esophageal Cancer
Esophageal cancer is the seventh most common cancer globally and the sixth leading cause of cancer-related deaths. The 5-year relative survival rate for patients with metastatic esophageal cancer is generally less than 8%. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, accounting for 90% and 10% of all cases, respectively. Each year, there are approximately 572,000 new diagnosed cases, and about 500,000 people die from esophageal cancer. Most patients are diagnosed at an advanced stage, which significantly impacts their daily lives, including their ability to eat. The incidence of esophageal cancer is highest in Asia, with over 444,000 new cases annually, accounting for approximately 80% of global cases.
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Note: Nivolumab (Opdivo®，nivolumab) approved only in mainland China for the treatment of epidermal growth factor receptor (EGFR) gene mutation-negative and anaplastic lymphoma kinase (ALK) negative, locally advanced or metastatic non-small cell lung cancer with disease progression or intolerance after prior platinum-based chemotherapy (NSCLC) Adult patients.
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