The BATTLE trial: personalizing therapy for lung cancer.
The BATTLE trial: personalizing therapy for lung cancer.
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DOI：
10.1158/2159-8274.cd-10-0010
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发表时间：
2011-06
期刊：
影响因子：
28.2
通讯作者：
Hong WK
中科院分区：
文献类型：
--
作者：
Kim ES;Herbst RS;Wistuba II;Lee JJ;Blumenschein GR Jr;Tsao A;Stewart DJ;Hicks ME;Erasmus J Jr;Gupta S;Alden CM;Liu S;Tang X;Khuri FR;Tran HT;Johnson BE;Heymach JV;Mao L;Fossella F;Kies MS;Papadimitrakopoulou V;Davis SE;Lippman SM;Hong WK
肺癌是世界范围内导致死亡的主要癌症；大规模试验未能改善化疗难治性非小细胞肺癌（NSCLC）患者的临床结果。在初始等随机化期后，BATTLE根据新鲜核心针活检标本中NSCLC发病机制的分子生物标志物，将化疗难治性NSCLC患者适应性地随机分配到厄洛替尼、万德替尼、厄洛替尼+贝沙罗汀或索拉非尼。主要终点为8周时的疾病控制率（DCR）。在255名患者中，随机分配到厄洛替尼（59例）、万德替尼（54例）、厄洛替尼+贝沙罗汀（37例）和索拉非尼（105例），244名患者符合DCR分析。11.5%的患者发生肺活检后气胸，6.5%的患者发生治疗相关毒性3-4级。总体结果为8周DCR为46%，中位无进展生存期为1.9个月，中位总生存期为9个月，1年生存期为35%。预测治疗的DCR显著优越的个体标记包括：厄洛替尼的表皮生长因子受体（EGFR）突变（P=0.04）；厄洛替尼加贝沙罗汀组cyclin D1阳性（P=0.01）或EGFR扩增（P=0.006）；血管内皮生长因子受体2阳性（P=0.05）；无EGFR突变（P=0.01）或EGFR高多体（P=0.05）。在EGFR野生型患者中，索拉非尼与所有其他方案相比（64%对33%，P<0.001），在突变型kras患者中，与所有其他方案相比（61%对32%，P=0.11）， 8周DCR更好。与本研究中分析的单个生物标志物相比，预先指定的生物标志物组的预测性更低。作为首个在预处理NSCLC中完成的活检研究，BATTLE证实了我们预先设定的关于生物标志物和靶向治疗相互作用的假设，为NSCLC患者的个性化治疗建立了一个新的范例。（ClinicalTrials.gov编号：NCT00409968， NCT00411671, NCT00411632, NCT00410059, NCT00410189.）
Lung cancer is the leading cancer cause of mortality worldwide; large-scale trials have failed to improve clinical outcomes of patients with chemorefractory non-small-cell lung cancer (NSCLC). Following an initial equal randomization period, BATTLE adaptively randomized patients with chemorefractory NSCLC to erlotinib, vandetanib, erlotinib plus bexarotene, or sorafenib based on molecular biomarkers of NSCLC pathogenesis in fresh core needle biopsy specimens. The primary end point was disease control rate (DCR) at 8 weeks. Of 255 patients randomly assigned to erlotinib (59 patients), vandetanib (54), erlotinib plus bexarotene (37), and sorafenib (105), 244 were eligible for the DCR analysis. Pneumothorax after lung biopsy occurred in 11.5% and treatment-related toxicities grade 3–4 in 6.5% of patients. Overall results were a 46% 8-week DCR, 1.9-month median progression-free survival, 9-month median overall survival, and 35% 1-year survival. Individual markers predicting a significantly superior DCR for a treatment included: epidermal growth factor receptor (EGFR) mutation (P=0.04) for erlotinib; cyclin D1 positivity (P=0.01) or EGFR amplification (P=0.006) for erlotinib plus bexarotene; vascular endothelial growth factor receptor 2 positivity (P=0.05) for vandetanib; and absence of EGFR mutation (P=0.01) or of EGFR high polysomy (P=0.05) for sorafenib. A better 8-week DCR occurred with sorafenib versus all other regimens (64% versus 33%; P<0.001) among EGFR wild-type patients and versus all other regimens (61% versus 32%; P=0.11) among mutant-KRAS patients. The prespecified biomarker groups were less predictive than the individual biomarkers analyzed in this study. The first completed biopsy-mandated study in pretreated NSCLC, BATTLE confirmed our pre-specified hypotheses regarding biomarker and targeted treatment interactions, establishing a new paradigm for personalizing therapy for patients with NSCLC. (ClinicalTrials.gov numbers, NCT00409968, NCT00411671, NCT00411632, NCT00410059, NCT00410189.)