Comparison of efficacy and safety of salvage-line nivolumab monotherapy between 240 and 480 mg for advanced esophageal squamous cell carcinoma.

Abstract

317 Background: Nivolumab monotherapy was established as the standard second-line treatment of advanced esophageal squamous cell carcinoma (ESCC) based on the results of the ATTRACTION-3 trial. Initially, fixed dosing of 240 mg every two weeks (240) was used according to the results of the ATTRACTION-3 trial in Feb 2020. After that, fixed dosing of 480 mg every four weeks (480) was available in clinical practice according to pharmacokinetic data on advanced melanoma in Sep 2020. However, there were little data on the efficacy and safety of these dosing for advanced ESCC patients. Methods: We retrospectively reviewed data from ESCC patients who received nivolumab monotherapy for second or later-line at our institution. We evaluated progression-free survival (PFS), objective response rate (ORR), and the incidence rate of adverse events (AEs) compared between 240 and 480. Cox proportional regression model, Fisher’s exact tests, and t-tests were used for analysis. Results: We identified 117 patients as the subject of this study. Patients characteristics in 2nd line were as followed (240 vs 480); the median age (range): 68(46-85) vs 68.5(51-84) years old, PS (0/1/2): 34/61/5% vs 54/42/4%, taxane refractory cases: 18.6 vs 53.8%. In 3rd or later line; the median age (range): 63.5(47-85) vs 58(46-80) years old, PS (0/1/2): 28/60/12% vs 14/86/0%, taxane refractory cases: 72 vs 71.4%. The ORR were 11.9 vs 24.0% in 2nd line (p=0.19), and 0 vs 14.3% in 3rd or later line (p=0.22). The median PFS was 1.7 vs 4.1 months in 2nd line (HR = 0.60; [95% CI: 0.35-1.01; p = 0.056]), and 1.4 vs 1.8 months in 3rd or later line (HR = 0.58; [95% CI: 0.23-1.46; p = 0.25]). The all-grade AEs in 58.3 vs 69.7 were observed; rash 16.7 vs 6.1%, diarrhea 9.5 vs 6.1%, adrenal insufficiency 3.6 vs 6.1%, and interstitial pneumonia 3.6 vs 15.2%. There were no treatment-related deaths. Conclusions: In this study, fixed dosing of nivolumab in 240mg and 480mg showed comparable outcomes on efficacy and safety.