LANCET ONCOL :Selumetinib与多西他赛联合治疗KRAS基因突变晚期NSCLC疗效佳
2012-12-10 LANCET ONCOL LANCET ONCOL
多国联合研究显示，对于既往接受治疗的KRAS基因突变晚期非小细胞肺癌（NSCLC）患者，与单用多西他赛治疗相比，联用MEK抑制剂Selumetinib治疗效果更佳。论文11月28日在线发表于《柳叶刀·肿瘤学》（Lancet Oncol）。 该研究显示，Selumetinib组和安慰剂组的中位总生存（OS）期分别为9.4个月和5.2个月，中位无进展生存（PFS）期分别为5.3个月
多国联合研究显示，对于既往接受治疗的KRAS基因突变晚期非小细胞肺癌（NSCLC）患者，与单用多西他赛治疗相比，联用MEK抑制剂Selumetinib治疗效果更佳。论文11月28日在线发表于《柳叶刀·肿瘤学》（Lancet Oncol）。
该研究显示，Selumetinib组和安慰剂组的中位总生存（OS）期分别为9.4个月和5.2个月，中位无进展生存（PFS）期分别为5.3个月和2.1个月，客观缓解率为37%和0；两组3级及以上不良反应的发生率分别为82%和67%。
Background
No targeted therapies are available for KRAS-mutant non-small-cell lung cancer (NSCLC). Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers. We did a prospective, randomised, phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRAS-mutant NSCLC.
Methods
Eligible patients were older than 18 years of age; had histologically or cytologically confirmed stage IIIB—IV KRAS-mutant NSCLC; had failed first-line therapy for advanced NSCLC; had WHO performance status of 0—1; had not received previous therapy with either a MEK inhibitor or docetaxel; and had adequate bone marrow, renal, and liver function. Patients were randomly assigned (in a 1:1 ratio) to either oral selumetinib (75 mg twice daily in a 21 day cycle) or placebo; all patients received intravenous docetaxel (75 mg/m2 on day 1 of a 21 day cycle). Randomisation was done with an interactive voice response system and investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival, analysed for all patients with confirmed KRAS mutations. This study is registered with ClinicalTrials.gov, number NCT00890825.
Findings
Between April 20, 2009, and June 30, 2010, we randomly assigned 44 patients to receive selumetinib and docetaxel (selumetinib group) and 43 to receive placebo and docetaxel (placebo group). Of these, one patient in the selumetinib group and three in the placebo group were excluded from efficacy analyses because their tumours were not confirmed to be KRAS-mutation positive. Median overall survival was 9·4 months (6·8—13·6) in the selumetinib group and 5·2 months (95% CI 3·8—non-calculable) in the placebo group (hazard ratio [HR] for death 0·80, 80% CI 0·56—1·14; one-sided p=0·21). Median progression-free survival was 5·3 months (4·6—6·4) in the selumetinib group and 2·1 months (95% CI 1·4—3·7) in the placebo group (HR for progression 0·58, 80% CI 0·42—0·79; one-sided p=0·014). 16 (37%) patients in the selumetinib group and none in the placebo group had an objective response (p<0·0001). Adverse events of grade 3 or higher occurred in 36 (82%) patients in the selumetinib group and 28 (67%) patients in the placebo group. The most common grade 3—4 adverse events were neutropenia (29 [67%] of 43 patients in the selumetinib group vs 23 [55%] of 42 patients in the placebo group), febrile neutropenia (eight [18%] of 44 patients in the selumetinib group vs none in the placebo group), dyspnoea (one [2%] of 44 patients in the selumetinib group vs five [12%] of 42 in the placebo group), and asthenia (four [9%] of 44 patients in the selumetinib group vs none in the placebo group).
Interpretation
Selumetinib plus docetaxel has promising efficacy, albeit with a higher number of adverse events than with docetaxel alone, in previously treated advanced KRAS-mutant NSCLC. These findings warrant further clinical investigation of selumetinib plus docetaxel in KRAS-mutant NSCLC. 小提示：本篇资讯需要登录阅读，点击跳转登录
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本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
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#Lancet#
27
#Oncol#
28
#MET#
24
#联合治疗#
37
#KRAS#
27
#晚期NSCLC#
30
#KRAS基因#
36