PD-1 inhibitors combined with paclitaxel and cisplatin in first-line treatment of esophageal squamous cell carcinoma (ESCC): a network meta-analysis

Abstract

Background The combinations of PD-1 inhibitors with paclitaxel/cisplatinum (PD-1 + TP) and fluoropyrimidine/cisplatinum (PD-1 + FP) both have been shown to improve overall survival (OS) and progression-free survival (PFS) in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no consensus on which chemotherapy regimen combined with PD-1 has better efficacy. To deal with this important issue in the first-line treatment of patients with ESCC, a network meta-analysis (NMA) was performed. Methods Data were collected from eligible studies searched in Medline, Web of Science, PubMed, the Cochrane Library and Embase. The pooled hazard ratio (HR) for the OS, and PFS, odds ratio (OR) for the objective response rate (ORR) and ≥ 3 grade treatment-related adverse events (≥ 3TRAEs) were estimated to evaluate the efficacy of PD-1 inhibitors combined with TP or FP. Results Five RCTs and one retrospective study involving 3685 patients and evaluating four treatments were included in this NMA. Compared to other treatments, PD-1 + TP was better. For the PFS, the HRs for PD-1 + TP compared to PD-1 + FP, TP and FP were 0.59 (0.44, 0.80), 0.56 (0.51, 0.61) and 0.45 (0.37, 0.56) respectively. For the OS, PD-1 + TP was also a better treatment compared to other treatments. The HRs were 0.74 (0.56, 0.96), 0.64 (0.57, 0.71), 0.53 (0.43, 0.67) respectively. For the ORR, there was no significant difference between PD-1 + TP and PD-1 + FP, and the ORs were 1.2 (0.69, 2.11). Compare with TP and FP, PD-1 + TP had an obvious advantage, ORs were 2.5 (2.04, 3.04) and 2.95 (1.91, 4.63). For ≥ 3TRAEs, PD-1 + TP compared to other treatments, ORs were 1.34 (0.74, 2.46) and 1.13 (0.92, 1.38) and 2.23 (1.35, 3.69). Conclusion PD-1 + TP significantly improved both PFS and OS compared to PD-1 + FP. Taking into account both efficacy and safety, PD-1 + TP may be a superior first-line treatment option for ESCC.

PD-1 inhibitors in advanced esophageal squamous cell carcinoma: a survival analysis of reconstructed patient-level data

“…Different chemotherapy schemes may have different antitumor efficacies. In a meta-analysis by Zhao J., PD-1 inhibitors with paclitaxel/cisplatinum were superior to fluoropyrimidine/cisplatinum ( Zhao et al, 2023 ). Several studies reported that taxane induces immunogenic cell death of cancer cells and causes various immunogenic actions, which creates favorable conditions to enhance the immune response of PD-1 inhibitors ( Chan and Yang, 2000 ; Garnett et al, 2008 ; Galluzzi et al, 2020 ).…”

Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective

“…The breakthrough in understanding immune checkpoints and the subsequent advancement of drugs, particularly monoclonal antibodies targeting programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1), represents a pivotal moment in the landscape of cancer immunotherapy [ 384 ]. These treatments have exhibited robust and sustained antitumor effects across a spectrum of cancer types [ 385 , 386 , 387 ]. However, the challenge of a notably small response rate remains a significant bottleneck for anti-PD-1/PD-L1 therapies, aggravated by the absence of precise molecular markers for patient selection [ 388 , 389 , 390 ].…”