Esophageal cancer is a prevalent malignancy accounting for approximately 0.51 million new cases and 0.45 million fatalities in 2022, worldwide (Bray et al., 2024). Surgery remains the standard therapy for early-stage esophageal cancer patients, but most esophageal cancer patients are diagnosed at an advanced stage (Deboever et al., 2024; Sheikh et al., 2023). Despite the progress in the treatment of advanced esophageal cancer, the prognosis of these patients remains poor (He et al., 2021; Puhr et al., 2023; Siegel et al., 2025; Waters and Reznik, 2022). Thus, investigating potential treatments is crucial in improving the prognosis of advanced esophageal cancer patients.

Currently, programmed cell death-1 (PD-1) inhibitors have emerged as a crucial treatment regimen for advanced esophageal cancer (Shoji et al., 2024; Yang et al., 2023; Yang et al., 2024). PD-1 inhibitors exert their effect by inhibiting the interaction between PD-1 and its ligands, which enhances T cell activity, thereby strengthening the capability of the immune system to recognize and eliminate cancer cells (Yang et al., 2023). Previous studies have illustrated that several PD-1 inhibitors, such as nivolumab and pembrolizumab, have exhibited promising efficacy in various malignancies, including esophageal cancer (Doki et al., 2022; Janjigian et al., 2024; Janjigian et al., 2021; Rha et al., 2023; Sun et al., 2018; Sun et al., 2021).

Camrelizumab, a humanized high-affinity immunoglobulin G4-kappa monoclonal antibody targeting PD-1, has been developed to treat diverse cancers, including esophageal cancer (Markham and Keam, 2019). As reported by the ESCORT study, camrelizumab as a second-line treatment achieved objective response rate (ORR) and disease control rate (DCR) of 20.2% and 44.7% in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients (Huang et al., 2020). Additionally, the ESCORT-1^st study indicated that camrelizumab plus chemotherapy as a first-line treatment achieved progression-free survival (PFS) and overall survival (OS) of 6.9 months and 15.3 months in advanced or metastatic ESCC patients (Luo et al., 2021). Based on these promising outcomes from the pivotal clinical trials, camrelizumab has been recommended as a first or second-line treatment for advanced ESCC patients in the Chinese Society of Clinical Oncology (CSCO) guidelines. However, the strict selection criteria of the previous trials often exclude patients with poor performance status or prior treatments (common characteristics in clinical practice), limiting the generalizability of their results to broader patient populations.

Accordingly, this real-world study aimed to evaluate the efficacy and safety of camrelizumab-based regimens in patients with advanced esophageal cancer in real-world settings. In particular, this study provided additional evidence on the comparative outcomes of different camrelizumab-based combinations and explored prognostic factors associated with survival, thereby offering novel insights into the optimal real-world use of camrelizumab beyond controlled trial populations. We hypothesized that camrelizumab-based regimens would demonstrate acceptable efficacy and manageable safety, with combination therapy potentially conferring survival advantages over monotherapy in the real-world setting.

Camrelizumab-based regimens, such as camrelizumab monotherapy and camrelizumab plus chemotherapy or targeted therapy, achieve acceptable treatment response in esophageal cancer patients (Huang et al., 2020; Lu et al., 2025; Luo et al., 2021; Meng et al., 2024; Zhang et al., 2020). For example, camrelizumab combined with apatinib and chemotherapy as a first-line treatment achieved ORR and DCR of 80.0% and 96.7%, respectively, in advanced ESCC patients (Zhang et al., 2020). Additionally, the ESCORT-1^st study reported that camrelizumab plus chemotherapy as a first-line treatment achieved an ORR of 72.1% and a DCR of 91.3% in advanced or metastatic ESCC patients (Luo et al., 2021). Moreover, the CAP 02 Re-challenge study indicated that the ORR and DCR were 10.2% and 69.4% in advanced ESCC patients who had a history of immune checkpoint inhibitors (Meng et al., 2024). Overall, the previously reported range of ORR was 10.2%–80.0%, and the range of DCR was 69.4%–96.7% in advanced esophageal cancer patients receiving camrelizumab-based regimens (Huang et al., 2020; Lu et al., 2025; Luo et al., 2021; Meng et al., 2024; Zhang et al., 2020). In this study, the ORR and DCR were 18.8% and 84.4%, respectively, in advanced esophageal cancer patients. The ORR and DCR identified in this study were within the ranges reported by previous studies (Huang et al., 2020; Lu et al., 2025; Luo et al., 2021; Meng et al., 2024; Zhang et al., 2020). Therefore, in real-world clinical practice, camrelizumab-based regimens could exhibit potentially satisfactory efficacy in advanced esophageal cancer patients. According to previous real-world clinical studies, the ORR and DCR ranged from 15.1% to 72.0% and 35.8%–92.0% in advanced esophageal cancer patients receiving PD-1 inhibitor-based regimens (Kao et al., 2023; Kim et al., 2022; Makino et al., 2024). Compared to these data, camrelizumab appeared to show comparable efficacy to other PD-1 inhibitors. Therefore, camrelizumab might serve as a potential immunotherapy option for the treatment of advanced esophageal cancer.

PD-1 inhibitors have dramatically revolutionized the treatment landscape of esophageal cancer and prolonged the survival of patients (Shoji et al., 2024). According to previous studies, camrelizumab-based regimens achieved median PFS of 5.7–9.9 months and OS of 10.9–19.4 months in advanced esophageal cancer patients (Lu et al., 2025; Luo et al., 2021; Zhang et al., 2020). Similar to the findings of the previous studies, this study discovered that camrelizumab-based regimens achieved median PFS and OS of 6.8 and 17.4 months in advanced esophageal cancer patients. Some real-world clinical studies reported that PD-1 inhibitor-based regimens achieved median PFS of 1.9–9.8 months and OS of 6.4–20.3 months in advanced esophageal cancer patients (Kao et al., 2023; Kim et al., 2022; Makino et al., 2024). Compared to these real-world data, camrelizumab seemed to provide similar survival outcomes to other PD-1 inhibitors. In real-world clinical practice, the strategies of camrelizumab-based regimens are largely different, with camrelizumab plus chemotherapy being the most frequently prescribed regimen for advanced esophageal cancer patients (Lu et al., 2025). Therefore, it is meaningful to explore the impact of camrelizumab-based treatment strategies on the survival of advanced esophageal cancer patients. We found that PFS was prolonged in advanced esophageal cancer patients receiving camrelizumab combination therapy compared to those receiving camrelizumab monotherapy. In detail, compared with patients receiving camrelizumab monotherapy, PFS was longer in patients receiving camrelizumab plus chemotherapy, camrelizumab plus apatinib, and camrelizumab plus chemotherapy and apatinib. According to previous evidence, we speculated that camrelizumab, apatinib, and chemotherapy might possess a synergistic anti-tumor effect, which could reprogram the immunosuppressive tumor microenvironment, thereby achieving a better PFS compared to camrelizumab alone (Li et al., 2022; Ramakrishnan and Gabrilovich, 2011). Regarding OS, it seemed to be prolonged in patients receiving camrelizumab combined with other regimens compared to those receiving camrelizumab monotherapy, but it did not achieve statistical significance. The inconsistency between PFS and OS outcomes might be as follows: (1) the sample size in each subgroup was small, limiting the statistical power. (2) the improvement in PFS reflected earlier disease control, while OS was influenced by multiple post-progression factors, such as subsequent systemic therapy, patient performance status, and tumor heterogeneity. The presence of these factors might inhibit the translation of PFS improvement in OS.

Furthermore, we explored independent factors associated with PFS and OS in advanced esophageal cancer patients. (1) ECOG PS score was independently related to a shorter PFS in advanced esophageal cancer patients. A possible explanation would be that patients with a higher ECOG PS score tended to have difficulty tolerating cancer treatments, such as immunotherapy-based treatments, resulting in a poor PFS in these patients (Zhang et al., 2021). (2) Camrelizumab plus apatinib (vs. camrelizumab monotherapy) was independently associated with a longer PFS in advanced esophageal cancer patients. A reason behind this could be that camrelizumab plus apatinib could synergistically enhance anti-tumor immune responses by increasing the ratio of cluster of differentiation (CD)8⁺ cytotoxic T cells to forkhead box protein 3⁺ Treg cells, the accumulation of CD20⁺ B cells, and the T-helper (Th)1/Th2 cytokine ratio, which led to a prolonged PFS (Zhang et al., 2021). (3) Concomitant disease was independently related to a longer OS in advanced esophageal cancer patients. However, more evidence is required to validate this finding. (4) TNM stage was independently associated with a poor OS in advanced esophageal cancer patients. Advanced TNM stage reflected a greater tumor burden (Marom, 2022). Therefore, patients with advanced TNM stage might benefit less from camrelizumab-based regimens, leading to a poor OS.

The incidence of adverse events following camrelizumab-based regimens ranged from 73.0% to 100.0% in advanced esophageal cancer patients according to previous studies (Lu et al., 2025; Luo et al., 2021; Meng et al., 2022; Zhang et al., 2020). Most common adverse events were anemia, alopecia, decreased neutrophil count, increased alanine aminotransferase level, decreased white blood cell count, anorexia, and fatigue (Lu et al., 2025; Luo et al., 2021; Zhang et al., 2020). However, in this study, the incidence of adverse events was 71.4% in advanced esophageal cancer patients receiving camrelizumab-based regimens, which was slightly lower than the data in previous studies. We speculated that this discrepancy might be attributable to the inherent limitations of real-world studies, where adverse event reporting was primarily driven by clinical relevance, potentially leading to underreporting of mild or transient adverse events. In this study, the most frequently encountered adverse events were fatigue, anorexia, and leukopenia. The majority of adverse events were grade 1-2 (64.0%). The incidence of grade 3-4 adverse events was relatively low (7.3%). Additionally, immune-related adverse events, such as RCCEP and hypothyroidism, were also observed in this study, with the overall incidence of 7.8% and 6.8%, respectively. Most of these two immune-related adverse events were grade 1-2, suggesting that they were mild to moderate and manageable. Overall, our findings suggested that camrelizumab-based regimens appeared to be generally safe and tolerable, but further large-scale studies are needed to confirm their safety profile.

Although promising findings were discovered in this study, limitations could not be omitted. (1) The single-arm design hindered us from comparing the efficacy and safety of camrelizumab-based regimens with other treatments, such as chemotherapy, in advanced esophageal cancer patients, which in turn limited our capacity to attribute the observed therapeutic effects solely to the treatment itself. (2) Our study presented real-world insights into the use of camrelizumab-based regimens in advanced esophageal cancer patients. However, this study was conducted in China, which restricted the generalizability of our findings. (3) We conducted subgroup analyses to explore the advantages of specific camrelizumab-based regimens in prolonging the survival of advanced esophageal cancer patients. Nevertheless, the sample size in each subgroup was relatively small, which might restrain the statistical power. (4) Some eligibility criteria in this study were based on investigators’ subjective judgment, which reflected common practice in real-world clinical settings. However, such subjective judgment might introduce selection bias. (5) Due to the observational nature of the study, confounding factors may have influenced the results. (6) Patients in this study received different camrelizumab-based regimens. This treatment heterogeneity, while reflective of real-world clinical practice, may have contributed to variability in efficacy and safety outcomes. (7) No prior statistical justification was performed, which might limit confidence in the negative findings of the survival analyses.

In conclusion, camrelizumab-based regimens achieve a median PFS and OS and 6.8 and 17.4 months, respectively, with an adverse event incidence of 71.4%, in advanced esophageal cancer patients. In clinical practice, the camrelizumab combination regimens may prolong PFS compared with its monotherapy; however, these findings are based on subgroup analyses with limited sample size and should be interpreted cautiously. Further validation in larger, controlled, and prospective studies is warranted to confirm these observations.