Opdivo demonstrates statistically significant overall survival benefit versus chemotherapy in patients with advanced esophageal cancer.- BMS + Ono Pharma

Bristol-Myers Squibb Company and Ono Pharmaceutical Co., Ltd.announced results from the Phase III ATTRACTION-3 trial evaluating Opdivo (nivolumab) versus chemotherapy (docetaxel or paclitaxel) for the treatment of patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs.

For the primary endpoint of overall survival (OS), Opdivo demonstrated a statistically significant improvement over chemotherapy, with a 23% reduction in risk of death [Hazard Ratio (HR) 0.77; 95% Confidence Interval (CI): 0.62 to 0.96; p=0.019] and a 2.5-month improvement in median OS [10.9 months (95% CI: 9.2 to 13.3)] compared to patients treated with chemotherapy [8.4 months (95% CI: 7.2 to 9.9)]. The safety profile of Opdivo in this trial was consistent with previously reported studies in ESCC and other solid tumors. These data (Presentation #LBA11) will be featured in the Presidential Symposium on Monday, September 30 from 4:30-6:15 PM CEST at the European Society for Medical Oncology (ESMO) 2019 Annual Congress in Barcelona, Spain and simultaneously published in The Lancet Oncology.

Patients treated in the Opdivo arm showed 12- and 18-month OS rates of 47% (95% CI: 40 to 54) and 31% (95% CI: 24 to 37), respectively, versus 34% (95% CI: 28 to 41) and 21% (95% CI: 15 to 27) among patients in the chemotherapy arm. Survival benefit with Opdivo was observed regardless of tumor PD-L1 expression levels. An exploratory analysis of patient-reported outcomes showed significant overall improvement in quality of life with Opdivo versus chemotherapy.

The objective response rates (ORR) between the two arms were comparable at 19% (95% CI: 14 to 26) among patients receiving Opdivo versus 22% (95% CI: 15 to 29) among those receiving chemotherapy. However, the study showed Opdivo substantially increased the median duration of response (DoR) for patients [6.9 months (95% CI: 5.4 to 11.1) versus 3.9 months (95% CI: 2.8 to 4.2)]. Seven patients in the Opdivo arm had ongoing responses at data cutoff compared to two patients in the chemotherapy arm. An overall HR of 1.08 (95% CI: 0.87 to 1.34) suggested no meaningful difference in progression-free survival (PFS) between the Opdivo and chemotherapy arms.

�These are very promising results for patients with advanced esophageal squamous cell carcinoma for whom prognosis is typically poor and are particularly important given Opdivo improved survival regardless of PD-L1 status,� said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. �We are encouraged to see important progress being made in this tumor type and look forward to broadening our research in gastrointestinal tumors.�

Fewer treatment-related adverse events (TRAEs) were reported with Opdivo versus chemotherapy, with a rate of 66% of any grade TRAEs for patients receiving Opdivo compared to 95% for patients receiving chemotherapy. Patients in the Opdivo arm also experienced a lower incidence of Grade 3 or 4 TRAEs compared to those in the chemotherapy arm (18% versus 63%), and the percentage of patients experiencing TRAEs leading to discontinuation was the same in both arms (9%).