pembrolizumab 495位病人 整體反應率是19.4% 整體存活率中間值是12個月
以前未有治療的病人 101位病人 反應率是24.8% 存活率中間值是16.2個月
以前有治療的病人 394位病人 反應率是18% 存活率中間值是9.3個月
9.5%的病人有3級以上的不良事件(AE) 1位病人因pembrolizumab引發的肺炎死亡
病人有PD-L1表象50%以上 反應率是45.2%
The multi-arm phase I KEYNOTE-001 trial evaluated the humanized IgG4 kappa isotype PD-1 antibody pembrolizumab as monotherapy in patients with both systemic therapy–naive and treatment-refractory NSCLC (n = 495).[3] Across all patients, the ORR was 19.4%, the median duration of response was 12.5 months, and the median OS was 12 months. Among previously untreated patients, the median OS was 16.2 months and the ORR was 24.8% (n = 101). Among previously treated patients, the median OS was 9.3 months and the ORR was 18% (n = 394). Grades 3 to 5 treatment-related AEs were reported in 9.5% of all patients, with one fatal case of pneumonitis. This study found that tumor PD-L1 status positivity, defined as samples with more than 50% of cells staining positive, was correlated with ORR (reported as 45.2%), median OS (not reached), and median progression-free survival (mPFS; 6.3 months).
第三期實驗 pembrolizumab 與 docetaxel 歐洲紫杉醇比較 病人PD-L1表象1%以上
整體存活率中間數是10.4-12.7個月 vs 8.5個月 (化療)
3級以上不良事件(AE) 13-16% vs 35%(化療)
pembrolizumab的整體表現讓FDA批准pembrolizumab上市
The phase II/III KEYNOTE-010 trial evaluated pembrolizumab at two doses compared with docetaxel in previously treated patients with PD-L1–positive advanced or metastatic NSCLC.[4] In this study, PD-L1 positivity was defined as tumors with more than 1% of cells staining positive. This study found a significant improvement in median OS among patients in both pembrolizumab arms (10.4 months at the 2-mg/kg dose and 12.7 months at the 10-mg/kg dose) compared with those in the docetaxel arm (8.5 months); there was no statistical improvement in PFS in the pembrolizumab arms. However, among the patients with more than 50% of tumor cells staining positive, both median OS (14.9 to 17.3 months vs 8.2 months with docetaxel) and PFS (5 to 5.2 months vs 4.1 months with docetaxel) were significantly improved in the pembrolizumab arms. Rates of grade 3–5 treatment-related AEs were less common with pembrolizumab (13% and 16% at the 2- and 10-mg/kg doses, respectively) than with docetaxel (35%). Together, these two studies, along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, led to the FDA approval of pembrolizumab as therapy for patients with previously treated PD-L1–positive advanced or metastatic NSCLC.[16]
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