Abstract CT075: Updated overall survival outcomes from a randomized, double-blind phase III study of sintilimab versus placebo in combination with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma (ORIENT-15)

Abstract Background: The ORIENT-15 study (NCT03748134) evaluated sintilimab (anti-PD-1 antibody) plus chemotherapy (Sin+Chemo) versus placebo plus chemotherapy (Chemo) as first-line (1L) treatment of unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC). At the prespecified interim analysis, this study met the primary endpoints of overall survival (OS) in all patients (pts) (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.51-0.78; P<0.001) and the pts with PD-L1 combined positive score (CPS) ≥10 (HR 0.64; 95% CI 0.48-0.85; P=0.002) (Lu, et al. BMJ 2022). Here we report the updated OS results with an extended follow-up time. Methods: Eligible pts were randomized 1:1 to receive sintilimab/placebo (3 mg/kg in pts weighing <60 kg or 200 mg in pts weighing ≥60 kg, IV Q3W) for up to 24 months plus chemo (paclitaxel 175 mg/m2 Q3W plus cisplatin 75 mg/m2 Q3W as TP regimen, or cisplatin 75 mg/m2 Q3W plus 5-FU 800 mg/m2 on days 1-5 Q3W as CF regimen). Stratification factors were PD-L1 expression (tumor proportion score <10% or ≥10%), ECOG PS (0 vs 1), liver metastasis (presence vs absence), and chemo regimen (TP vs CF). The primary endpoints were OS in the pts with PD-L1 CPS ≥10 and all pts. Results: Overall, 690 pts (median age 63.0; 85.5% male; 93.3% Asian and 4.9% White; 24.3% liver metastasis; 90.7% TP regimen) were randomized and received Sin+Chemo (341 pts) or Chemo (349 pts). As of data cutoff date (Aug 28, 2022), the median follow-up was 32.2 months (interquartile range 28.0-35.8); 231 OS events were observed in Sin+Chemo group and 278 in Chemo group. Sin+Chemo continued to demonstrate an OS benefit vs Chemo in all pts (median OS 17.4 [95% CI 16.0-19.8] vs 12.8 [95% CI 11.3-14.5] months; HR 0.661 [95% CI: 0.554-0.788]; P<0.0001), and the pts with PD-L1 CPS ≥10 (18.4 [95% CI 16.2-24.6] vs 14.5 [95% CI 11.7-16.4] months; HR 0.635 [95% CI 0.503-0.803]; P=0.0001). Estimated OS rates at 12 and 24 months for Sin+Chemo vs Chemo in all pts were 64.0% vs 53.5% and 41.4% vs 22.9%, respectively. Subgroup analyses of OS in all pts were generally consistent with the previous report, showing homogeneity in OS outcomes. The CTCAE grade ≥3 treatment-related adverse events occurred in 60.7% pts in Sin+Chemo group and 56.2% pts in Chemo group. No new or unexpected safety signals were observed. Conclusions: Sin+Chemo continued to demonstrate significant OS benefits in advanced ESCC in both overall and PD-L1 CPS ≥10 populations with an acceptable safety profile over time. These data further support the use of Sin+Chemo as a standard of care for 1L treatment in these patients. Citation Format: Zhihao Lu, Junye Wang, Yongqian Shu, Li Kong, Buhai Wang, Lei Yang, Guochun Cao, Guogui Sun, Yinghua Ji, Hu Liu, Tongjian Cui, Wensheng Qiu, Aziz Zaanan, Roberto Pazo Cid, Hui Zhou, Xing Sun, Yan Wang, Yuling Chen, Haoyuan Li, Lishi Zhang, Lin Shen. Updated overall survival outcomes from a randomized, double-blind phase III study of sintilimab versus placebo in combination with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma (ORIENT-15) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT075.