Nivolumab (Opdivo) 肺線癌實驗數據 (August 2016)－探索癌症

nivolumab 整體存活率中間值是9.9個月反應率是17%　其中3 mg/kg劑量效果最佳　整體存活率中間值是14.9個月反應率是24%　

nivolumab最亮麗的表現是反應的持久性 1 年整體存活率是56% 2年整體存活率是42% 3 年整體存活率是27% 這種結果在以前是從未聽說過的

此外10%的病人病情穩定至少6個月這些病人得到nivolumab治療的效益卻沒有表現在RECIST定義的反應率數據上

多數病人對治療耐受性佳 14%的病人有3級以上的不良事件(AE) 3位病人因nivolumab引發的肺炎死亡

For all nivolumab doses, median overall survival (OS) was 9.9 months and the ORR was 17%; nivolumab at 3 mg/kg, the dose selected for further investigation, yielded a median OS of 14.9 months and an ORR of 24%. Perhaps most encouraging was the duration of response: at the 3-mg/kg dose, the 1-, 2-, and 3-year OS rates were 56%, 42%, and 27%, respectively—survival outcomes that were previously unheard of in this heavily pretreated patient population. For the 17% of patients who had objective responses, the estimated median duration of response was 17 months. The authors also noted that an additional 5% of patients had unconventional patterns of immune responses, in that the tumor kinetics showed a reduction in target lesions in the presence of new lesions, or regression of target lesions after initial growth. Another 10% of patients had stable disease lasting at least 6 months. This indicated that patients were receiving clinical benefit from nivolumab that was not necessarily included in the classic Response Evaluation Criteria in Solid Tumors (RECIST)-based response rate. Although the treatment was found to be well tolerated overall, with a 14% rate of grade 3/4 treatment-related AEs, three treatment-related deaths associated with pneumonitis were reported.

第三期實驗 nivolumab 與 docetaxel 歐洲紫杉醇比較鱗狀細胞NSCLC 272位病人

反應率是20% vs 9% 整體存活率中間數是9.2個月 vs 6個月

1年存活率42% vs 24%　

3級以上不良事件(AE) 7% vs 55%

另一個第三期實驗 nivolumab 與化療歐洲紫杉醇比較非鱗狀細胞NSCLC 582位病人

反應率是19% vs 12% 整體存活率中間數是12.2個月 vs 9.4個月(化療)

1年存活率是51% vs 39%(化療)

3級以上不良事件 10% vs 54%(化療) 1位病人因nivolumab引發的肺炎死亡

nivolumab的整體表現讓FDA批准nivolumab上市

The phase III CheckMate 017 trial evaluated nivolumab vs docetaxel in previously treated patients with advanced or metastatic squamous NSCLC (n = 272).[1] The ORRs were 20% vs 9%, respectively. Survival outcomes were also statistically significantly improved: median OS was 9.2 months with nivolumab vs 6 months for patients treated with docetaxel. The 1-year OS rates were 42% vs 24%, and the rates of treatment-related grade 3/4 AEs were 7% vs 55% for nivolumab and docetaxel, respectively. CheckMate 057, a similar phase III trial, compared nivolumab vs docetaxel in patients with previously treated advanced or metastatic nonsquamous NSCLC (n = 582).[2] Again, both ORR (19% vs 12%) and median OS (12.2 months vs 9.4 months) were significantly improved in the nivolumab arm. In addition, the 1-year OS rates were 51% in the nivolumab group vs 39% in the docetaxel group, and the rates of grade 3/4 treatment-related AEs were 10% with nivolumab vs 54% with docetaxel. One treatment-related death, attributed to encephalitis, occurred in the nivolumab arm. Interestingly, positive PD-L1 membrane staining was associated with greater treatment efficacy in the nonsquamous study population (CheckMate 057),[2] but not in the squamous study population (CheckMate 017).[1] Taken together with the other previously described study results, these investigations led to FDA approval of nivolumab monotherapy in previously treated advanced or metastatic NSCLC.[15]