Zhengzheng Xia ¹ Zhuoshi Lian ¹ Huali Xie ² Ziyuan Zhou ¹ Tujia Chen ³ Jun Meng ^1* Jun Yang ⁴

• ¹ Department of pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
• ² Department of Pharmacy, Shenzhen Hospital, The University of Hong Kong, Shenzhen, Guangdong Province, China
• ³ Department of Pharmacy, Boai Hospital of Zhongshan, Zhongshan, China
• ⁴ Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Background: Programmed cell death protein 1 (PD-1) inhibitors are now commonly used worldwide in the management of non-small cell lung cancer (NSCLC). However, it remains unclear whether pembrolizumab and sintilimab, two of the most widely used PD-1 inhibitors in China, have significant differences in their effects on patients with NSCLC . To compare the effectiveness and safety profiles of pembrolizumab and sintilimab in advanced NSCLC patients undergoing comprehensive therapy, a multicenter retrospective cohort study was designed and implemented using propensity-score matching (PSM) analysis. Methods: A total of 225 patients who received comprehensive therapy including pembrolizumab (n=127) or sintilimab (n=98),from January 1 to December 31, 2020, and met the eligibility criteria were included. PSM analysis (1:1) was performed to balance potential baseline confounding factors. For both treatments, Kaplan-Meier analysis and Cox regression were employed to compare 1-year progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR) and rates of all adverse events (AEs). Results: The PSM analysis resulted in 63 matched pairs of patients. After PSM , the median PFS was 8.68 months in the sintilimab group and 9.46 months in the pembrolizumab group. The 1-year PFS showed no significant difference between the pembrolizumab and sintilimab groups before and after PSM (P=0.873 and P=0.574, respectively). Moreover, within the matched cohort, the pembrolizumab group had an ORR of 30.2% and a DCR of 84.1%, while the sintilimab group exhibited an ORR of 41.3% and a DCR of 88.9%. There were no significant differences in ORR and DCR between the two groups (P=0.248 and P=0.629, respectively). The incidence of grade 3 or 4 treatment-related AEs was significantly higher in pembrolizumab group than in sintilimab group (42.9% vs. 33.3%, P=0.043). Multivariable Cox proportional hazards regression analysis indicated that lines of treatment and regimens significantly influenced the PFS of patients (P < 0.05). Conclusions: This study presents a similar effectiveness between sintilimab and pembrolizumab in the treatment of patients with advanced NSCLC, with sintilimab potentially displaying a superior clinical safety profile. Clinical trial registration: Identifier is MR-44-23-000113.