RESUMEN
BACKGROUND: With the increasing use of immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC), there remains an unmet need for options to address disease progression after prior ICIs. This single-arm phase II study evaluated the efficacy and safety of re-challenge with camrelizumab plus apatinib in patients with advanced ESCC who were previously treated with ICIs. METHODS: This study enrolled patients aged 18-75 years with unresectable locally advanced, locally recurrent, or distant metastatic ESCC who received prior ICIs. Patients received intravenous camrelizumab 200 mg every 2 weeks and oral apatinib 250 mg daily until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was the investigator-assessed confirmed objective response rate (ORR). RESULTS: Between September 1, 2021 and March 29, 2023, 49 eligible patients were enrolled and received treatment. Among the 49 patients, the confirmed ORR was 10.2 % (95 % CI 3.4-22.2), the disease control rate (DCR) was 69.4 % (54.6-81.7), the median progression-free survival (PFS) was 4.6 months (95 % CI 3.8-6.5) and overall survival (OS) was 7.5 months (5.5-13.6). Grade ≥ 3 treatment-related adverse events occurred in 17 patients (34.7 %). No treatment-related deaths occurred. CONCLUSIONS: This study showed that the confirmed ORR was modest and did not reach clinically meaningful improvement for patients with ESCC who were previously treated with ICIs, with a manageable safety profile.
RESUMEN
Objectives: Recently, there has been extensive research on dual immunotherapy for advanced or metastatic non-small cell lung cancer (NSCLC), yet a comprehensive evaluation is lacking. This study aimed to rank the available treatment options and assess the efficacy and safety of dual immunotherapy regimens through the implementation of a Bayesian network meta-analysis (NMA). Materials and methods: A thorough search was conducted to recognize eligible randomized controlled trials (RCTs) on March 20, 2023. Overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were evaluated to identify the efficacy and safety of dual immunotherapy regimens. The surface under the cumulative ranking curve (SUCRA) and P score were employed to rank the treatments. Results: Eleven clinical trials involving six different regimens were included in this study. The combination of anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) antibodies with anti-T-cell immunoglobulin and ITIM domain (TIGIT) antibodies emerged as the most promising regimen for improving OS and PFS, followed by anti-PD-1/PD-L1 + anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) + chemotherapy treatment and anti-PD-1/PD-L1 + anti-CTLA-4 treatment. The forest plots demonstrated that these three regimens were all superior to chemotherapy. The above results were observed in both unselected treatment line and first-line settings. The least likely to be associated with TRAEs and grade ≥3 TRAEs were respectively anti-CTLA-4 treatment and anti-PD-1/PD-L1 + anti-TIGIT treatment, with anti-PD-1/PD-L1 + anti-CTLA-4 + chemotherapy treatment to be the worst. Conclusions: This NMA validated the promising efficacy and safety of dual immunotherapy in advanced or metastatic NSCLC. Among them, anti-PD-1/PD-L1 + anti-TIGIT regimen emerges as a highly potential therapeutic approach. Ongoing research efforts should focus on improving treatment regimens, identifying biomarkers, and managing TRAEs to optimize the patient benefits of dual immunotherapy.