Zhang Huiqiang, Jin Xiao, Bian Li
Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Transl Breast Cancer Res. 2023 Sep 22;5:1. doi: 10.21037/tbcr-23-33. eCollection 2024.
Toripalimab (JS001) is a monoclonal antibody against programmed cell death-1 (PD-1), independently developed by Shanghai Junshi Biosciences Co., LTD, which is the first domestic original PD-1 inhibitor approved in China. TORCHLIGHT is the first phase III trial of PD-1 inhibitor combined chemotherapy in advanced triple-negative breast cancer (TNBC) in China, evaluating the efficacy and safety of toripalimab plus nab-paclitaxel as first- or second-line therapy. Nab-paclitaxel has significant advantages over other chemotherapy drugs, as paclitaxel nanoparticles combine with natural albumin to increase drug delivery and bioavailability of paclitaxel. Firstly, nab-paclitaxel has a higher therapy response; Secondly, albumin carries paclitaxel out of the blood circulation faster, reducing the damage to normal tissues, ensuring the survival of more normal immune cells and exerting immune efficacy. Finally, nab-paclitaxel does not cause allergic reactions caused by organic solvents and does not require glucocorticoid pretreatment, avoiding immune suppression and ensuring the maximum efficacy of immune checkpoint inhibitors (ICIs). In TORCHLIGHT trial, 95% of subjects were on the first line treatment, with only 5% being on the second line, and 56% patients were programmed death-ligand 1 (PD-L1) positive in total population. It achieved the survival benefits of progression-free survival (PFS) and overall survival (OS) dual efficacy end points, which stood out among numerous ICIs in advanced TNBC. TORCHLIGHT trial, as the name of it, like a torch to more patients with advanced TNBC, lighting up their lives. We described the design background of TORCHLIGHT trial and reviewed primary trials of PD-1 or PD-L1 inhibitor in advanced TNBC both domestically and internationally.
托瑞帕利单抗（JS001）是一种抗程序性细胞死亡蛋白1（PD-1）的单克隆抗体，由上海君实生物科技有限公司自主研发，是中国首个获批的国产原研PD-1抑制剂。TORCHLIGHT研究是中国首个针对晚期三阴性乳腺癌（TNBC）开展的PD-1抑制剂联合化疗的III期试验，旨在评估托瑞帕利单抗联合白蛋白结合型紫杉醇作为一线或二线治疗的疗效和安全性。白蛋白结合型紫杉醇相较于其他化疗药物具有显著优势，因为紫杉醇纳米粒与天然白蛋白结合，可提高紫杉醇的药物递送和生物利用度。首先，白蛋白结合型紫杉醇具有更高的治疗反应率；其次，白蛋白能更快地将紫杉醇带出血液循环，减少对正常组织的损伤，确保更多正常免疫细胞存活并发挥免疫功效。最后，白蛋白结合型紫杉醇不会引起有机溶剂导致的过敏反应，也无需糖皮质激素预处理，避免了免疫抑制，确保免疫检查点抑制剂（ICI）发挥最大疗效。在TORCHLIGHT试验中，95%的受试者接受一线治疗，仅5%接受二线治疗，总体人群中56%的患者程序性死亡配体1（PD-L1）呈阳性。该试验实现了无进展生存期（PFS）和总生存期（OS）双重疗效终点的生存获益，在众多晚期TNBC的ICI中脱颖而出。TORCHLIGHT试验，正如其名，像火炬一样为更多晚期TNBC患者照亮生命之路。我们描述了TORCHLIGHT试验的设计背景，并回顾了国内外晚期TNBC中PD-1或PD-L1抑制剂的主要试验。
