晚期NSCLC维持治疗策略.ppt

1、晚期NSCLC维持治疗策略,中山医科大学肿瘤医院 张 力,晚期肺癌治疗的模式,诊断,缓解或稳定,PD,死亡,1线化疗 (4-6周期),2-3线化疗,问题1： 为什么要停下来休息?,继续一线两药化疗药物直到6个周期,Socinski MA, et al. J Clin Oncol 2002;20:13351343.Park JO, et al. J Clin Oncol 2007;25:52335239. von Plessen et al. Br J Cancer 2006;95:966973. Park JO, et al. J ClinOncol 2007;25:52335239,继续一线

2、两药化疗药物直到6个周期,Smith et al：6周期=31%,Socinsk et al: 6周期=13%,Park et al：6周期=68%,Von Plessen et al: 6周期=54%,一线化疗因为毒性退出化疗的比例,Socinski MA, et al. J Clin Oncol 2002;20:13351343,一线化疗时间的Meta分析,JCO 2009; 27:3277-3283,ASCO Guideline的变化,1997,2004,2009,ASCO Educational Book 2003,问题： 停下来休息的后果是什么？,晚期肺癌治疗的模式,诊断,缓解或稳定

3、,PD,死亡,1线化疗 (4-6周期),2-3线化疗,？,病人 : 肿瘤治疗好了吗？ 医生：没有！ 病人 : 以后不用再治疗了吗？ 医生：不是！,晚期肺癌治疗的模式,诊断,缓解或稳定,PD,死亡,1线化疗 (4-6周期),2-3线化疗,？,病人 : 什么时候再回来治疗？ 医生：。,晚期NSCLC维持治疗研究中对照组PFS结果汇总,Fidias JCO 27:591-8,2009 Ciuleanu Lancet 374:1432-40,2009 Capuzzo Lancet Oncol 11:521-529,2010 J Clin Oncol 29: 2011 (suppl; abstr CRA

4、7510) Belani,ASCO 2010,Perol,ESMO,2010 Ciuleanu, et al. The Lancet 2009 Cappuzzo, et al. ASCO 2009 Zhang L, et al. 2011 ASCO Abstract 7511.,近50%患者无法进入二线治疗,主要原因 PS差(58%)一线治疗疗效差 (24%)合并症 (24%)痌变范围 (22%),29% 仅接受 BSC,接受一线治疗的患者,100%,54%,接受二线治疗的患者,来自306位欧盟医师的资料,46% 未接受二线治疗,17% 死亡,TNS Healthcare, Brand Tra

5、cking Study, December 2007,100 80 60 40 20 0,多个III期临床研究中，30%的患者未接受二线治疗,1. J Clin Oncol 2002;20:133543; 2. J Clin Oncol 2003;21:293339; 3. Lung Cancer 2006;52:15563;4. Br J Cancer 2006;95:96673; 5. J Thorac Oncol 2007;2(Suppl. 4):S666 (Abs. P2-235);6. J Clin Oncol 2007;25:523339; 7. Lancet 2009;374:1

6、43240; 8. J Clin Oncol 2008;26(Suppl. 15):6s (Abs. 3); 9. J Clin Oncol 2008;26:354351; 10. J Clin Oncol 2009;27:59198,0255075100,Socinski et al. 20021 Belani et al. 20032 Brodowicz et al. 20063 von Plessen et al. 20064 Barata et al. 20075 Park et al. 20076 Ciuleanu et al. 20097 Pirker et al. 20088 S

7、cagliotti et al. 20089 Fidias et al. 200910,接受二线治疗的患者(%),In our opinion, treatment-free intervals remain an option; however, patients must be observed closely with serial radiographic examinations because the median PFS is approximately 2 to 3 months. The optimal timing and method of observing patie

8、nts for disease progression are unclear, and patients should be informed of the risks associated with a treatment-free interval.,一线化疗后停下来休息,Stinchcombe, Socinski, JTO 2011,问题： 有没有其他的治疗选择？,诊断,一线治疗含铂两药化疗 (46周期),CR/PR/SD,新的治疗模式：维持治疗,进展前尽可能拖延无进展生存期 缓解症状复发或恶化 改善总生存期,晚期NSCLC维持治疗的不同治疗策略,晚期NSCLC维持治疗PFS结果汇总,

9、Fidias JCO 27:591-8,2009 Ciuleanu Lancet 374:1432-40,2009 Capuzzo Lancet Oncol 11:521-529,2010 J Clin Oncol 29: 2011 (suppl; abstr CRA7510) Belani,ASCO 2010,Perol,ESMO,2010 Ciuleanu, et al. The Lancet 2009 Cappuzzo, et al. ASCO 2009 Zhang L, et al. 2011 ASCO Abstract 7511.,INFORM研究中的PFS,Zhang L, et

10、al. 2011 ASCO Abstract 7511.,8.5 易瑞沙 (n=105),2.6 安慰剂 (n=104),中位 PFS (月),AstraZeneca Data On File.,16.6 易瑞沙 (n=15),2.8 安慰剂 (n=15),中位 PFS (月),4.8 易瑞沙 (n=148),2.6 安慰剂 (n=148),中位 PFS (月),HR = 0.42,HR = 0.17,全组人群,腺癌亚组,EGFR M+亚组,Odds Ratio=3.31(95% CI 1.60-6.82, p=0.0012). 中位症状恶化时间(LCS): 4.3月(gefitinib) v

11、 2.3月(placebo).,INFORM生活质量改善,Han BH, et al WCLC 2011,晚期NSCLC维持治疗OS结果汇总,Fidias JCO 27:591-8,2009 Ciuleanu Lancet 374:1432-40,2009 Capuzzo Lancet Oncol 11:521-529,2010 J Clin Oncol 29: 2011 (suppl; abstr CRA7510) Belani,ASCO 2010,Perol,ESMO,2010 Ciuleanu, et al. The Lancet 2009 Cappuzzo, et al. ASCO 2

12、009 Zhang L, et al. 2011 ASCO Abstract 7511.,问题： 如何解释没有OS的改善？,维持治疗研究的设计,SATURN研究,Cappuzzo, et al. ASCO 2009,Coudert,etal.ELCC2010,Randomized studies on first line EGFR TKI in patients with EGFR mutation,Mok et al NEJM 2009, Lee et al WCLC 2009, Mitsudomi et al Lancet Oncology 2010, Maemondo NEJM 201

13、0 Zhou et al ESMO 2010，Rosell et al ASCO 2011,JMEN 研究的后续治疗,Ciuleanu, et al. The Lancet 2009,IFCT-GFPC 0502研究,PerolM,etal.ESMO:abstr370PD.,二线培美曲塞的治疗情况,Perol M, et al. J Clin Oncol 2010 ; 28(s) : abstr 7507.,IFCT-GFPC 0502研究,全组病人,接受二线治疗的病人,Perol M, et al. J Clin Oncol 2010 ; 28(s) : abstr 7507.,Real-W

14、orld Considerations for Maintenance Therapy,JTO 2011; 6: 365371,Because patients with stage IV NSCLC have longer OS in clinical trials, the impact of any one drug, or the timing of its use, on that survival becomes more difficult to detect as patients receive sequential therapies. This complexity wi

15、ll increase the importance of PFS as an end point in future clinical trials of novel drugs in patients with stage IV NSCLC.,JCO 2011,问题： 怎样实现个体化维持治疗?,如何合理地选择维持治疗？,哪些患者适合维持治疗？ 原药维持和换药维持如何选择？ 怎样实现个体化维持治疗?,两项吉西他滨维持治疗研究显示:对PS评分好的患者进行维持治疗疗效显著,*与安慰剂相比,ASCO 2010 M. Perol, et al., Abstract # 7507 ASCO 2010

16、C. P. Belani, et al., Abstract # 7506,培美曲塞: 中位 =3.9个月 (3.0-4.2) 安慰剂: 中位 =2.6个月 (2.2-2.9) Log-rank P=0.0002 未调整HR: 0.64 (0.51-0.81),JNEN,Paramount,Time （months）,Time （months）,Progression-free probability,病理类型对选择培美曲赛维持治疗的,从延长 PFS角度来看，两种治疗方式都是合理的选择。,Ciuleanu, et al. The Lancet 2009,SD的患者更适合换药维持,Ciulean

17、u, et al. The Lancet 2009,Cappuzzo, et al. ASCO 2009,EGFR TKIs: EGFR mut+的病人,Cappuzzo et al. Lancet Oncol 2010; Brugger, et al. WCLC 2009,维持治疗目标争取更多的病人能够接受后续的治疗 尽可能地延长患者PFS。 改善/保持较好的生活质量 (QoL) 副作用小的药物更加适合作为维持治疗的选择。 很多因素影响患者的OS。,维持治疗用于晚期NSCLC总体评价,1. “Switch maintenance” Tx with erlotinib or pemetrexe

18、d following completation of first-line CT is an option. Decision factors for the use of “switch maintenance” include histology, type and response to first line chemotherapy, residual toxicity, patients symptoms and preference. 2. Any patient whose tumor harbour an EGFR activating mutation should receive EGFR TKIs as maintenance, if not yet received as first-line. Strength of recommendation: B; Level of evidence: I,总 结,For patients with stable disease or response after four cycles, immediate treatment with alternative, single-agent chemotherapy such as pemetrexed in patients with no