阿帕替尼用于一线治疗进展后晚期非鳞非小细胞肺癌的疗效和生存分析

背景与目的 晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的二线、三线化疗有效率较低,靶向药物的应用为部分患者带来生存获益.阿帕替尼是一种新型小分子抗血管生成药物,在多种恶性肿瘤治疗中展现出令人满意的抗癌活性.本研究旨在评价阿帕替尼用于一线治疗进展后晚期非鳞NSCLC的安全性和疗效.方法 回顾性分析128例晚期非鳞NSCLC不同治疗组患者的疗效和生存情况,用Kaplan-Meier法和Cox模型进行分析.结果 以单纯化疗组为对照,阿帕替尼单药组、单纯化疗组和阿帕替尼联合化疗组的中位无进展生存期(progression free survival,PFS)分别为3.0个月(P=0.381)、3.7个月和6.0个月(P<0.001),中位总生存期(overall survival,OS)分别为6.0个月(P=0.494)、6.5个月和9.0个月(P=0.001).3级-4级不良反应发生率分别为18.5%、15.8%和16.0%(P=0.947).治疗方案(P=0.018)及体能状态(performance status,PS)(P<0.001)是PFS的独立影响因素,吸烟史(P=0.014)、治疗方案(P=0.002)和PS(P<0.001)是OS的独立影响因素.结论 阿帕替尼安全性高,肺癌一线治疗失败后,二线或三线化疗联合阿帕替尼,与单纯化疗相比,患者有PFS和OS获益,阿帕替尼单药与单纯化疗组间PFS和OS无明显差异;无吸烟史、PS 0分-1分和联合治疗的患者预后更好.     

101例难治性小细胞肺癌的二线治疗生存分析

摘 要：［目的］探讨含铂双药化疗和单药化疗用于难治复发小细胞肺癌（small cell lung cancer,SCLC）患者二线化疗的疗效及安全性。［方法］ 回顾性分析101例难治性SCLC患者二线治疗的疗效和生存情况,并采用Cox多因素分析模型进行预后相关因素的分析。［结果］单药和双药组有效率(response rate,RR) 分别为2.9%和7.5%(P=0.208),疾病控制率 (disease control rate,DCR) 分别为14.7%和59.7%(P<0.001),中位无进展生存期(progression-free survival,PFS)分别为1.23个月和2.77个月(P<0.001)。两组中位总生存期(overall survival,OS)差异无统计学意义(5.40个月vs 5.93个月,P=0.988)。Ⅲ~Ⅳ度不良反应单药组比双药组发生率低(20.6% vs 52.2%,P=0.007)。多因素分析显示体能状况评分(performance status,PS)（HR=1.491,P=0.002）是PFS的独立影响因素。［结论］双药治疗可延长部分患者的PFS,但不良反应相对增加。     

细胞因子诱导的杀伤细胞治疗87例非小细胞肺癌临床疗效评价

  目的   评价细胞因子诱导的杀伤细胞（cytokine-induced killer cells,CIK）联合化疗治疗非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效。   方法   收集天津医科大学附属肿瘤医院2003年1月至2008年3月接受CIK细胞联合化疗治疗的87例NSCLC患者作为联合治疗组,接受单纯化疗的87例NSCLC患者作为对照组。Ⅰ~ⅢA期为早期,Ⅳ期为晚期。配对因素包括性别、年龄、吸烟情况、病理类型、KPS评分、临床分期、是否手术、乳酸脱氢酶（lactate dehydrogenase,LDH）、血小板、血红蛋白、治疗情况等。观察终点为无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）。对于未取得中位OS或PFS组用平均OS或PFS表示。   结果   联合治疗组与单纯化疗组2年PFS率分别为47%、36%（P < 0.05）,2年OS率分别为71%、43%（P < 0.001）。两组患者中位PFS分别为24、12个月（P < 0.05）,中位OS分别为48、18个月（P=0.001）。早期患者中联合治疗组与单纯化疗组2年PFS率、中位PFS差异无明显统计学意义（74% vs. 58%,P=0.138;57个月vs. 45个月,P=0.093）,联合治疗组2年OS率及中位OS明显高于单纯化疗组（92% vs. 72%,P < 0.05;73个月vs. 53个月,P < 0.05）。晚期患者中联合治疗组与单纯化疗组2年PFS率分别为13%、5%（P < 0.001）,2年OS率分别为42%、3%（P < 0.001）,两组患者中位PFS分别为13、6个月（P=0.001）,中位OS分别为24、10个月（P=0.001）。多因素分析显示临床分期及CIK治疗周期数是联合治疗组肺癌患者的独立预后因素。   结论   CIK细胞联合化疗能够延长肺癌患者的总体生存时间,并延长晚期患者的无进展生存时间,显著改善肺癌患者预后。CIK细胞治疗多于7个周期者疗效更好。      

免疫检查点抑制剂治疗EGFR-TKI耐药晚期非小细胞肺癌的疗效及不良反应

目的:探讨免疫检查点抑制剂(immune checkpoint inhibitor,ICI)治疗表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)耐药晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及不良反应。方法:收集2015年1月至2019年3月在解放军总医院接受ICI治疗的EGFR-TKI耐药晚期NSCLC患者临床资料,采用统计学方法分析EGFR-TKI耐药晚期NSCLC患者免疫治疗疗效及不良反应,阐明临床特征与免疫治疗疗效和患者预后的关系。结果:联合治疗较单药治疗者肿瘤客观缓解率(objective response rate,ORR)显著提高(28.6%vs.7.1%,P<0.01)。肿瘤分化差、联合治疗及年龄>60岁者分别较肿瘤分化好(5.1个月vs.2.8个月,P=0.030)、单药治疗(6.8个月vs.2.3个月,P<0.001)及年龄≤60岁者(7.1个月vs.4.7个月,P=0.020)无进展生存期(progression free survival,PFS)延长。联合治疗、肿瘤治疗缓解者分别较单药治疗(26.9个月vs.7.1个月)、肿瘤稳定者和进展者(30.8个月vs.18.7个月vs.12.8个月)总生存期(overall survival,OS)延长(P<0.001)。多因素分析显示年龄>60岁和联合治疗是PFS独立保护性因素(P<0.001)。联合治疗组的总体不良反应发生率较单药治疗组升高,但≥3级不良反应发生率两组间无显著性差异(P=0.28)。结论:ICI单药治疗EGFR-TKI耐药晚期NSCLC患者的疗效较差,而联合治疗能显著提高疗效,改善患者的预后。尽管联合治疗的总体不良反应发生率较高,但大体上不良反应可控。     

联合奥沙利铂或顺铂二线治疗晚期非小细胞肺癌的临床研究

背景与目的：晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)二线化疗可选择单药多西他赛或培美曲塞,联合铂类能否提高疗效及延长生存尚不明确。本研究比较单药多西他赛或培美曲塞与联合奥沙利铂或顺铂方案二线治疗晚期NSCLC近期疗效、生存期和安全性。方法：经一线联合顺铂或卡铂治疗失败的121例晚期NSCLC患者按3∶2∶1比例随机分组,对照组(n=56)：多西他赛75 mg/m2(所有肺癌)或培美曲塞500 mg/m2(非鳞癌),第1天;顺铂组(n=45)：顺铂25 mg/m2,第1~3天联合多西他赛或培美曲塞;奥沙利铂组(n=20)：奥沙利铂130 mg/m2,第1天联合多西他赛或培美曲塞。3周为1个周期,治疗每个周期评价不良反应,每2个周期评价疗效,回访生存期。结果：3组的治疗疾病反应率、无进展生存期(progression free survival,PFS)、总生存期(overall survival,OS)及不良反应差异均无统计学意义(P＞0.05)。≥60岁老年患者较＜60岁患者PFS更长(HR=0.56,95%CI：0.35~0.90,P=0.015);PS评分0~1分患者PFS和OS更长(HR=1.52,95%CI：1.01~2.30,P=0.048;HR=1.90,95%CI：1.17~3.09,P=0.009)。治疗反应率与PFS和OS相关(HR=2.93,95%CI：2.01~4.26,P=0.000;HR=2.03,95%CI：1.37~3.01,P=0.000)。化疗后发生贫血患者PFS和OS呈缩短趋势(HR=1.59,95%CI：0.97~2.61,P=0.066;HR=1.60,95%CI：0.94~2.75,P=0.085),血小板减少患者OS更短(HR=2.97,95%CI：1.01~8.78,P=0.049)。有神经毒性患者PFS呈缩短趋势(HR=3.36,95%CI：0.92~12.25,P=0.066)。二线治疗失败后接受后续治疗者OS有获益(HR=0.36,95%CI：0.22~0.61,P=0.000)。结论：二线联合奥沙利铂或顺铂治疗NSCLC患者疗效和生存期无提高。疾病反应、PS评分与PFS及OS相关,治疗后发生贫血、血小板减少、神经毒性患者预后可能更差。二线治疗失败后接受后续治疗能延长生存期。     

吉西他滨顺铂联合索拉非尼或安慰剂一线治疗晚期非小细胞肺癌的随机对照研究

背景与目的新药含铂两药联合治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效已达到平台期,本研究采用前瞻性随机对照的方法比较了吉西他滨顺铂联合索拉非尼或安慰剂一线治疗晚期NSCLC的疗效和安全性。方法经细胞学或病理学证实的30例晚期NSCLC患者随机进行吉西他滨顺铂联合索拉非尼或安慰剂治疗,化疗不超过6个周期,有效或稳定的患者继续服用索拉非尼或安慰剂,直至疾病进展或不能耐受不良反应。结果实验组(索拉非尼联合化疗组)和对照组(单纯化疗组)的分布基本平衡,两组有效率(response rate,RR)分别为55.6%和41.7%(P=0.905);两组的中位无疾病进展时间(progress-free survival,PFS)相似,分别为5个月和4个月(P=0.75);两组的中位生存时间(overall survival,OS)均为18个月,无统计学差异(P=0.68)。不良反应可耐受,实验组的高血压和腹泻发生率较对照组高。Cox多因素回归分析显示,身体状况好(ECOG评分为0分)、肺癌分期早(IIIb期)、无肝转移和后续进行酪氨酸激酶抑制剂(tyrasine kinasis inhibitor,TKI)治疗的患者生存明显延长,提示这些因素为良好的预后因素。结论在常规吉西他滨顺铂化疗的基础上增加靶向药物索拉非尼并未增加RR、PFS以及OS,后续类似研究需谨慎选择合适的患者。     

敏感复发小细胞肺癌二线化疗疗效及生存分析

目的:本研究旨在比较拓扑替康、含铂联合化疗和其他单药化疗用于敏感复发小细胞肺癌(small-celllung cancer,SCLC)患者二线化疗的疗效和安全性。方法:回顾性分析83例敏感复发SCLC患者接受二线化疗的疗效和生存情况,并采用COX比例风险模型进行预后的相关因素分析。结果:拓扑替康组、含铂联合化疗组和其他单药化疗组的中位无进展生存期(progression-free survival,PFS)分别为2.80、4.07和1.93个月(P=0.007),二线化疗后的中位总生存期(overall survival,OS)分别为8.07、10.57和7.27个月(P=0.021),Ⅲ～Ⅳ度不良反应发生率分别为47.6%、69.2%和30.0%(P=0.033)。COX比例风险模型分析结果显示,一线化疗疗效(有效与稳定/进展:风险比为1.27,P=0.013)、二线化疗前体能状况评分(0～1分与2分:风险比为1.36,P=0.019)和二线化疗前肿瘤分期(局限期与广泛期:风险比为2.16,P=0.006)是二线化疗OS的独立影响因素。结论:一线化疗有效、体能状况评分为0～1分、二线化疗前局限期患者更能从二线化疗中获益。与拓扑替康和其他单药化疗相比,二线含铂联合化疗的PFS和OS更具优势。     

KRAS突变晚期非小细胞肺癌分子分型、治疗及预后分析

目的:分析晚期Kirsten鼠类肉瘤(Kirsten rat sarcoma,KRAS)突变非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床病理特征、分子分型、治疗及预后。方法:回顾性分析2019年01-2022年01我院33例晚期KRAS+NSCLC患者的临床病理资料。分析KRAS亚型、TP53共突变及不同治疗方案和生存预后的相关性。结果:33例晚期KRAS+NSCLC患者,男性大约占90.9%（30/33);KRAS p.G12C突变为最常见分子分型,约42.4%（14/33）;另外,KRAS p.G12C突变人群对比其他KRAS突变患者,无进展生存期（progression-free survival,PFS)(6.5个月 vs 7.0个月;P=0.799)和总生存(overall survival,OS)(18.0个月 vs 24.0个月;P=0.266)均未见显著差异。亚组分析中,免疫联合化疗对比化疗+抗血管和单一化疗,可延长PFS(13.5个月 vs 7.5个月 vs 5.5个月;P=0.033),但OS却未见差异(25.0个月 vs 18.0个月 vs 25.0个月;P=0.854)。KRAS+/TP53+ NSCLC对比KRAS+/TP53-NSCLC,显著缩短PFS(5.5个月 vs 7.5个月;P=0.019)和OS(18.0个月vs 28.0个月;P=0.004)。多因素分析发现TP53共突变（HR=3.394;P=0.005）、治疗方案（HR=0.473;P=0.003）为PFS的预后因素;TP53共突变（HR=8.235;P=0.004）为OS的独立预后因素。结论:中国人群中,晚期KRAS+NSCLC患者男性较为多见,p.G12C为最常见分子分型。免疫治疗联合化疗可能延长晚期KRAS+NSCLC的PFS,但仍需进一步探索;TP53共突变可能为晚期KRAS+NSCLC不良预后因素。晚期NSCLC中KRAS和TP53共突变患者的治疗及预后需要进一步探索。     

TKI耐药后晚期EGFR突变型非小细胞肺癌对不同治疗的反应及预测性标志物的研究

  目的  评估TKI耐药后晚期EGFR突变型非小细胞肺癌（non-small cell lung cancer,NSCLC）在真实世界中化疗、化疗联合抗血管和免疫治疗的临床疗效以及最佳免疫治疗联合方案和探讨优势人群临床病理特征。  方法  回顾性分析2014年1月至2022年10月于广东省人民医院肿瘤医院收治229例TKI耐药后晚期EGFR突变型NSCLC患者的临床病理资料。本研究将纳入的患者分为非ICI治疗组（化疗和化疗联合抗血管）122例,ICI治疗组（含免疫治疗）107例,分析患者临床特征与治疗疗效之间的关系。  结果  纳入患者非ICI治疗组和ICI治疗组的中位无进展生存期（progression-free survival,PFS）分别为5.2个月和5.2个月（P=0.129）,中位生存期（overall survival,OS）分别为18.2个月和14.1个月（P=0.026）。进一步分析107例ICI治疗组,使用化疗联合免疫治疗、化疗联合抗血管联合免疫治疗和免疫单药或抗血管联合免疫治疗的中位PFS分别为5.6、6.7和2.3个月（P=0.074）,中位OS分别为15.5、18.6和8个月（P=0.165）。PD-L1表达≥50%患者的中位PFS和中位OS较PD-L1表达<50%患者明显延长（中位PFS:5.6个月vs. 5.0个月,P=0.040;中位OS:19.2个月vs. 12.6个月,P=0.046）。  结论  晚期EGFR突变型NSCLC患者TKI耐药后四药联合免疫治疗似乎呈现出更好的生存获益趋势,PD-L1表达是预测该人群免疫治疗获益的生物标志物。      

帕博利珠单抗治疗复发/转移性头颈部鳞状细胞癌患者的预后与营养因素的相关性分析

  目的  探究接受帕博利珠单抗二线治疗复发/转移性（recurrent/metastatic, R/M）头颈部鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）患者的临床相关营养因素与预后的相关性。  方法  回顾性分析2019年1月至2021年6月上海交通大学医学院附属第九人民医院收治的86例接受帕博利珠单抗治疗的R/M HNSCC患者,对其进行生存预后分析和危险因素评估。  结果  中位随访时间11.6（3.0～25.9）个月,中位总生存期（overall survival,OS）11.3个月,中位无进展生存期（progression-free survival,PFS）8.3个月。多因素分析显示,体质量不足（OS:P=0.016;PFS:P=0.003）、年龄≥60岁（OS:P=0.009;PFS:P=0.014）、低白蛋白（OS:P=0.013;PFS:P=0.010）、体力状态（PS）评分≥2分（OS:P＜0.001;PFS:P=0.005）、联合阳性评分（CPS）<1（OS:P=0.009;PFS:P=0.006）及临床分期rⅣ期（OS:P=0.011;PFS:P=0.003）是死亡风险增加的独立风险因素。超重是减少死亡风险的指标（OS:P=0.001;PFS:P=0.004）。Kaplan-Meier生存曲线分析显示,BMI及血清白蛋白与OS及PFS显著相关（P<0.001）。  结论  BMI、年龄、血清白蛋白、PS评分、CPS评分、临床分期与接受帕博利珠单抗治疗的R/M HNSCC患者预后显著相关,可作为R/M HNSCC患者抗PD-1治疗的独立预后预测指标。      

Third-line therapy for advanced non-small-cell lung cancer patients: feasible drugs for feasible patients

The proven benefit of third-line treatment in advanced non-small cell lung cancer (NSCLC) is still unclear. We retrospectively evaluated the outcome of advanced NSCLC patients treated with third-line therapies in our institution, especially focusing on efficacy and toxicity between mono-therapy and doublets chemotherapy, aiming to assess the value of third-line treatment and evaluate the efficacy of different regimens in third-line treatment. Three hundred and seventeen patients received a second-line treatment among 620 advanced NSCLC after failure of first-line chemotherapy. One hundred and twenty-six patients from this group were offered third-line or further-line treatments. Survival analysis was conducted based on Kaplan-Meier method, and Chi-square was used to compare data between second-line and third-line group. There were significant differences in overall survival between second-line and third-line treatments (17.70 months vs. 24.03 months, P < 0.0001). Twenty-four patients received single chemotherapy, epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) were used to treat thirty-three patients and sixty-nine patients received doublet chemotherapy in third-line treatment. The progression-free survival (PFS) after third-line therapy was 2.37 months in all patients and 2.30 months, 2.80 months, 2.97 months, in the doublet chemotherapy, single-agent chemotherapy, and EGFR-TKIs arms, respectively (P = 0.033). Cancer-related symptom relief improvement was confirmed in 78.9% patients (60/78). Forty-eight patients had no symptoms as confirmed by imaging examination. Patients with advanced NSCLC could get benefits from third-line treatments. Those patients could obtain a moderate progression-free survival and conspicuous improvement in the cancer-related symptom. Mono-therapy was recommended in third-line treatment.     

Efficacy and toxicity of pemetrexed as a third-line treatment for non-small cell lung cancer

Objective: Pemetrexed has been approved for second-line treatment in non-smallcell lung cancer (NSCLC). However, the role of third-line pemetrexedtherapy in NSCLC has not yet been generally accepted. We attemptedto validate third-line pemetrexed therapy and evaluate predictivefactors for pemetrexed therapy for NSCLC. Methods: Medical records of NSCLC patients who received pemetrexed therapythat progressed after systemic therapy were reviewed retrospectively.We stratified patients according to clinicopathologic characteristicsto find predictive factors for pemetrexed therapy. Results: A total of 100 patients were eligible for analysis, and overallprogression-free survival (PFS) was 3.03 months. The objectiveresponse rate was 12%, and the toxicity profile was favorable.Pemetrexed was used as a second-line treatment in 30% of patients,and as third- or further-line treatment in 70%. Comparing theefficacy of pemetrexed in these two settings (second-line versusthird- or further-line), there was no significant differencein terms of PFS (3.07 versus 2.83 months, P = 0.86). When weevaluated predictive factors by multivariate analysis, performancestatus significantly influenced PFS. Conclusions: Pemetrexed is a suitable third-line treatment option with goodefficacy and tolerable toxicity profile for NSCLC.     

Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.     

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

Both platinum-based doublet chemotherapy （PBC） and epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） prolong the survival of patients with advanced non-small cell lung cancer （NSCLC）. In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival （OS）. Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria： in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase Ill clinical trials--involving 11,456 adult patients in 32 arms--were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian （predominantly Caucasian） populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs （r = 0.797, P 〈 0.001）. The correlation was obvious in the trials in Asian populations （r= 0.936, P 〈 0.001） but was not statistically significant in the trials in predominantly Caucasian populations （r = 0.116, P = 0.588）. These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalJtJes available for therapy.     

对比EGFR-TKIs治疗EGFR突变状态未明晚期NSCLC疗效研究

目的探讨对比表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)一线、维持及二线治疗EGFR突变状态未明晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)的疗效。方法回顾性分析接受EGFR-TKIs治疗的57例EGFR突变状态未明晚期NSCLC,按照接受EGFR-TKIs治疗的时机分为EGFR-TKIs治疗一线组(19例)、维持组(18例)和二线组(20例),按照RECIST标准进行疗效评价。结果一线组、维持组和二线组客观有效率(52.6%vs 38.9%vs 35.0%,P=0.098)、中位无进展生存期(4.0月vs 7.8月vs 2.2月,P=0.417)差异无统计学意义,但一线组患者总生存期较维持组和二线组差(8.7月vs 20.0月vs 19.1月,P=0.009)。结论 EGFR突变状态未明晚期NSCLC EGFR-TKIs一线、维持和二线治疗的客观有效率和中位无进展生存期相似,但EGFR-TKIs一线治疗总生存期较短,建议EGFR-TKIs用于维持或二线治疗EGFR突变状态未明晚期NSCLC。     

多西他赛或表皮生长因子受体酪氨酸激酶抑制剂二线治疗晚期非小细胞肺癌的临床观察

目的 观察多西他赛或表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs）二线治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效及安全性。 方法 回顾性分析2009年1月至2013年6月接受多西他赛或EGFR-TKIs二线治疗晚期NSCLC患者的临床资料,对符合入组标准的100例进行观察和分析,其中52例接受EGFR-TKIs治疗（TKIs组）,48例接受多西他赛治疗（DOC组）。采用Kaplan-Meier方法计算两组患者的中位无疾病进展生存时间（mPFS） 、中位总生存时间（mOS）,并行Log-rank检验。结果 TKIs组、DOC组患者二线治疗后mPFS分别为6个月、3个月（P=0.021）;mOS分别为16个月、10个月（P=0.068）;客观有效率（ORR）分别为23.1％、6.3％（P=0.038）。DOC组Ⅲ~Ⅳ级白细胞减少、中性粒细胞减少及其引起发热的发生率明显高于TKIs组（P均＜0.001）。结论 临床上对具有EGFR敏感突变潜在临床特征的晚期NSCLC患者进行二线治疗时,EGFR-TKIs比多西他赛治疗能显著延长患者中位无疾病进展生存时间,毒副反应较少,具有更高的安全性。     

Long-term chemotherapy may prolong survival in advanced non-small-cell lung cancer among responders to first-line chemotherapy

Survival in patients with advanced non-small-cell lung cancer (NSCLC) has substantially improved. Long-term chemotherapy with epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) and other agents has been associated with long survival. We retrospectively examined the associations between overall survival (OS) and clinical variables in patients with advanced NSCLC who received at least one dose or course of outpatient chemotherapy in our institution. Of 360 patients who received first-line chemotherapy between January 1, 2004 and December 31, 2007, 185 subsequently received additional outpatient chemotherapy and 175 underwent inpatient chemotherapy only. Of the 185 patients, 147 (79.5%), 96 (51.9%), and 60 (32.4%) received second-line, third-line, and fourth-line chemotherapy, respectively. Patients who received outpatient chemotherapy had significantly longer median OS (22.3 months) than did those undergoing inpatient chemotherapy only (7.6 months; P < 0.0001). In univariate analysis of the 185 patients, sex, performance status (PS), smoking status, stage, best response to first-line chemotherapy, use of docetaxel, and EGFR-TKIs were significantly associated with OS (P values: 0.0019, 0.0066, 0.0001, 0.0231, 0.0011, 0.0250, and 0.0023, respectively). In multivariate analysis, PS, stage, best response to first-line chemotherapy, and use of docetaxel were significantly associated with OS (P values: 0.0272, 0.0030, 0.0022, and 0.0376, respectively). Survival was significantly longer among patients who responded to docetaxel and/or EGFR-TKIs. Long-term chemotherapy did not increase cumulative hospitalization. In patients with advanced NSCLC, an effective long-term chemotherapy regimen might prolong survival in responders to first-line chemotherapy.     

全脑放疗时间对EGFR突变非小细胞肺癌脑转移患者生存的影响

背景与目的全脑放疗（whole brain radiotherapy, WBRT）在表皮生长因子受体（epidermal growth factor receptor,EGFR）突变的非小细胞肺癌（non-small cell lung cancer, NSCLC）脑转移患者治疗中何时应用尚无高级别的循证医学证据。本研究旨在探讨WBRT的参与时间对携有EGFR突变的NSCLC脑转移患者生存的影响。方法2009年8月-2015年5月在我院确诊的EGFR突变伴脑转移的晚期NSCLC共78例患者,均接受WBRT及EGFR酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitors, EGFR-TKIs）治疗的48例初治患者进入临床分析,采用Cox比例风险模型分析患者颅内无进展生存期（progression-free survival, PFS）及总生存期（overall survival, OS）的影响因素。结果全组患者颅内客观缓解率（objective response rate, ORR）为81.3%,颅内疾病控制率（disease control rate, DCR）为93.8%,中位颅内PFS为10个月,中位OS为18个月。颅内PFS的多因素分析显示,美国东部肿瘤协作组评分（Eastern Cooperative Oncology Group performance status, ECOG PS）0分-1分（HR=30.436,95%CI：4.721-196.211,P<0.001）及早期WBRT患者（HR=3.663,95%CI：1.657-8.098,P=0.001）的颅内PFS更佳。OS的多因素分析显示,ECOG PS 0分-1分（HR=57.607,95%CI：6.135-540.953,P<0.001）、早期WBRT（HR=2.757,95%CI：1.140-6.669,P=0.024）及立体定向放射外科（stereotaxic radio surgery, SRS）的应用（HR=5.964,95%CI：1.895-18.767,P=0.002）是患者OS的独立预后因素。结论早期WBRT联合TKIs治疗可改善EGFR突变的NSCLC脑转移患者的预后,尚有待大样本的前瞻性临床试验验证。