atezolizumab (MPDL3280A) 是anti–PD-L1藥品 第一期實驗 53位病人 反應率是21% 研究人員發現反應率與腫瘤附近的抑制性免疫細胞(T reg, MDSC, tumor assoicated DC cells, Tumor associated Macrophage) 是否呈現PD-L1表象非常有關 與腫瘤癌細胞是否呈現PD-L1表象關係不大 13%的病人有3級以上的不良狀況
第二期實驗atezolizumab 與 docetaxel 歐洲紫杉醇比較 277位病人 存活期12.6個月 vs 9.7個月(化療) 3級以上的不良狀況11% vs 39%(化療)
Two trials have evaluated atezolizumab (MPDL3280A), a humanized IgG1 anti–PD-L1 antibody, in previously treated advanced or metastatic NSCLC. The first dose-escalation and expansion phase I study in multiple solid tumors included a 53-patient cohort with NSCLC.[17] In this subgroup of patients, the ORR was 21%. In this patient population, response to treatment with atezolizumab was found to be statistically significantly associated with tumor-infiltrating immune cell PD-L1 expression, but not tumor cell PD-L1 expression. The authors concluded that this suggested that PD-L1–suppressed preexisting immunity must be present in order to achieve an optimal response to PD-L1 blockade.[17] Across all patient cohorts, rates of treatment-related grade 3/4 AEs were observed in 13% of patients. The phase II POPLAR trial assessed efficacy and safety of atezolizumab vs docetaxel in previously treated advanced NSCLC, with patient stratification based on PD-L1 tumor-infiltrating immune cell status, tumor histology, and previous lines of therapy (n = 277).[18] OS was significantly improved in the atezolizumab population compared with the docetaxel population (12.6 months vs 9.7 months), and increasing improvement in OS was associated with increasing PD-L1 expression in tumor cells and/or tumor-infiltrating immune cells. This expression was defined differently and used a different assay compared with that used in the KEYNOTE trials; in the POPLAR trial it was defined via immunohistochemical scoring by PD-L1–expressing tumor-infiltrating immune cells as the percentage of tumor area: IC0 < 1%, IC1 ≥ 1% and < 5%, IC2 ≥ 5% and < 10%, and IC3 ≥ 10%; and as the percentage of PD-L1–expressing tumor cells: TC0 < 1%, TC1 ≥ 1% and < 5%, TC2 ≥ 5% and < 50%, and TC3 ≥ 50%. Treatment-related grade 3/4 AEs were seen in 11% of the atezolizumab-treated patients and in 39% of the docetaxel-treated patients, with one treatment-related death (from cardiac failure) in the atezolizumab group.
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