Effectiveness, safety, and patterns of use of camrelizumab in advanced esophageal cancer: an individual patient data pooled analysis of 987 patients from three prospective cohort studies

Cancer Immunology, Immunotherapy (2025) 74:138 https://doi.org/10.1007/s00262-025-03970-z RESEARCH Effectiveness, safety, and patterns of use of camrelizumab in advanced esophageal cancer: an individual patient data pooled analysis of 987 patients from three prospective cohort studies Zhihao Lu1 · Guoping Sun2 · Jiancheng Li3 · Jun Zhao4 · Zishu Wang5 · Dong Qian6 · Zhe Yang7 · Na Li8 · Junsheng Wang9 · Shuanghu Yuan10 · Yusheng Wang11 · Suyi Li12 · Zhen Yang13 · Fengming Ran14 · Yinghua Ji15 · Shaojin Zhu16 · Yanqiao Zhang17 · Chen Wang18 · Lixin Wan19 · Rongrong Zheng20 · Wenjie Deng20 · Fengzhuo Cheng20 · Lin Shen1 Received: 2 December 2024 / Accepted: 6 February 2025 © The Author(s) 2025 Abstract Background and aims This individual patient data pooled analysis aimed to evaluate the effectiveness, safety, and patterns of use of camrelizumab in a large cohort of advanced esophageal cancer (AEC) patients. Approach and results Adult patients (≥ 18 years) who had received camrelizumab as part of AEC treatment were pooled from three independent, prospective observational cohort studies (NCT04616040, ChiCTR1900027275, and ChiCTR2000039499). The main outcomes were patterns of camrelizumab use, progression-free survival (PFS), overall survival (OS), and safety in the overall population and specific subgroups of underrepresented patients. Among 987 patients, 450 (45.6%) received camrelizumab in the first line, 398 (40.3%) in the second line, and 139 (14.1%) in the third line or later. Most (69.7%) patients received camrelizumab plus chemotherapy regardless of treatment lines. The median PFS was 9.9 (95% CI 7.4, 14.4), 6.6 (95% CI 5.1, 8.8), and 5.7 (95% CI 3.1, 9.6) months in the first line, second line, and third line or later, respectively. The corresponding median OS was 15.5 (95% CI 12.6, 18.4), 12.1 (95% CI 10.0, 14.7), and 10.9 (95% CI 8.1, 14.5) months. Patients with poor performance status (ECOG PS ≥ 2) and with camrelizumab in the second line or later, but not patients with older age (≥ 75 years), were associated with poor survival. Adverse events occurred in 721 (73.0%) patients, with no new safety signals. Conclusions This study provides an overview of camrelizumab use in unselected AEC patients. The real-world effectiveness and safety of camrelizumab are generally consistent with those observed in pivotal trials. Keywords Esophageal cancer · Immunotherapy · Real-world · Overall survival Introduction Esophageal cancer is one of the leading causes of cancerrelated deaths worldwide, with approximately 511,000 new cases and 445,000 deaths in 2022 [1]. More than half of the new cases and deaths are estimated to occur in China [2]. Most patients diagnosed with esophageal cancer are at an advanced stage. The estimated 5-year survival rate is around 10–30% [3]. Immunotherapy with immune checkpoint inhibitors (ICIs) has changed the treatment landscape of patients with advanced esophageal cancer. Several programmed cell Zhihao Lu, Guoping Sun, and Jiancheng Li are co-first authors. Extended author information available on the last page of the article death protein 1 (PD-1) or its ligand (PD-L1) inhibitors, such as pembrolizumab and nivolumab, have been approved for clinical use [4–8]. Camrelizumab (SHR-1210), a humanized PD-1 monoclonal antibody, has been approved either alone or in combination by the National Drug Administration (NMPA) in China for the treatment of advanced or metastatic esophageal squamous cell cancer (ESCC). The phase III ESCORT-1st trial confirmed the efficacy and safety of camrelizumab in combination with paclitaxel and cisplatin chemotherapy for the first-line treatment of advanced or metastatic ESCC [9]. In addition, camrelizumab in combination with apatinib (a selective vascular endothelial growth factor receptor-2 [VEGFR-2] inhibitor) and chemotherapy (liposomal paclitaxel and nedaplatin) exhibited anti-tumor activity as the Vol.:(0123456789) 138 Page 2 of 12 first-line treatment in patients with advanced ESCC [10]. In the second-line setting, the phase III ESCORT trial demonstrated improved survival with camrelizumab monotherapy versus investigator-choice chemotherapy in patients with advanced or metastatic ESCC who had progressed on or were intolerant to prior first-line chemotherapy [11]. Moreover, camrelizumab in combination with apatinib showed promising activity and manageable safety as the second-line therapy in patients with advanced, recurrent or metastatic ESCC [12]. Based on these results, camrelizumab in combination with chemotherapy with or without apatinib has been recommended for the first-line treatment of advanced or metastatic esophageal cancer, while camrelizumab with or without apatinib has been recommended for the second-line treatment of advanced or metastatic esophageal cancer after progressed on prior first-line chemotherapy in the Chinese Society of Clinical Oncology (CSCO) guidelines. However, the real-world effectiveness and safety of camrelizumab in patients with advanced esophageal cancer treated in daily practice have not been extensively investigated. The available evidence is primarily based on patients meeting strict screening criteria and receiving predefined treatment regimens in pivotal clinical trials. It may not fully reflect real-world patient care practices and outcomes. Three prospective multicenter observational cohort studies have investigated the real-world effectiveness and safety of camrelizumab in patients with advanced esophageal cancer [13–15]. This study was therefore designed to pool individual patient data (IPD) from the above-mentioned three observational studies to further evaluate the real-world effectiveness, safety, and patterns of use of camrelizumab in a large sample of patients with advanced esophageal cancer. The IPD pooled analysis may not only provide more precision estimation but also enrich specific patients that are underrepresented in pivotal clinical trials (e.g., patients aged ≥ 75 years or with Eastern Cooperative Oncology Group [ECOG] performance status of ≥ 2). The findings of this study may help to better understand the current treatment practice and outcomes in advanced esophageal cancer patients across different treatment lines and those with specific clinical characteristics. Methods Study design and patients This was a pooled analysis of IPD from three independent, large-scale, prospective multicenter observational cohort studies in China (Trial 1: ESCORT-RWS/NCT04616040, Trial 2: NOAH-EC201/ChiCTR1900027275, and Trial 3: ChiCTR2000039499). The studies were similar in study design enabling post hoc pooled analysis (Supplementary Cancer Immunology, Immunotherapy (2025) 74:138 Table 1). All three studies were designed to evaluate the real-world effectiveness and safety of camrelizumab for the treatment of patients with unresectable locally advanced, recurrent, or metastatic esophageal cancer. All consecutive patients who met the eligibility criteria were scree (...truncated)