Local Consolidation Therapy (LCT) After First Line Tyrosine Kinase Inhibitor (TKI) for Patients With EGFR Mutant Metastatic Non–small-cell Lung Cancer (NSCLC)

Introduction

Although most NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutations have an impressive initial response, the vast majority has residual disease and develops acquired resistance after 9 to 14 months of EGFR tyrosine kinase (TKI) therapy. We recently reported a phase II trial showing that, for patients with molecularly unselected oligometastatic NSCLC who did not progress after first-line systemic therapy, local consolidation therapy (LCT) with surgery or radiation improved progression-free survival (PFS), compared with maintenance therapy alone. Herein, we report a retrospective analysis of LCT after TKI in patients with metastatic EGFR mutant NSCLC.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Versus Placebo as Maintenance Therapy for Advanced Nonsmall-cell Lung Cancer: A Meta-analysis of Randomized Controlled Trials

Background: Use of epidermal growth factor receptor inhibitors (EGFR-TKIs ) is now standard for nonsmall-cell lung cancer (NSCLC). However, the effects of EGFR-TKIs in maintenance therapy for advancedNSCLC patients are still unclear. The preent meta-analysis was performed to examine pooled data of randomizedcontrol trials (RCT) where EGFR-TKIs were compared against placebo in maintenance regimens for patientswith advanced NCSLC to quantify potential benefits and determine safety. Methods: Several data bases weresearched, including PubMed, EMBASE and CENTRAL, and we performed an internet search of conferenceliterature. The endpoints were objective response rates (ORR), progression-free survival (PFS) and overallsurvival (OS). We performed a meta-analysis of the published data, using Comprehensive Meta Analysis software(Version 2.0). with a fixed effects model and an additional random effects model, when applicable. The resultsof the meta-analysis are expressed as hazard ratios (HRs) or risk ratios (RRs), with their corresponding 95%confidence intervals (95%CIs). Results: The final analysis included six trials, covering 3,758 patients. Comparedwith placebo, EGFR-TKIs maintenance therapy improved ORR and PFS for patients with advanced NSCLC, thedifference being statistically significant (P<0.05), but proved unable to prolong patients’ OS. The main adversereactions were diarrhea and rashes. Conclusion: EGFR-TKIs demonstrated encouraging efficacy, safety andsurvival when delivered as maintenance therapy for patients with advanced NSCLC after first-line chemotherapy,especially for the patients who had adenocarcinomas, were female, non-smokers and patients with EGFR genemutations.     

Impact of Continuing First-Line EGFR Tyrosine Kinase Inhibitor Therapy Beyond RECIST Disease Progression in Patients with Advanced EGFR-Mutated Non-Small-Cell Lung Cancer (NSCLC): Retrospective GFPC 04-13 Study

Retrospective studies suggested a benefit of first-line tyrosine kinase inhibitor (TKI) treatment continuation after response evaluation in solid tumors (RECIST) progression in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. The aim of this multicenter observational retrospective study was to assess the frequency of this practice and its impact on overall survival (OS). The analysis included advanced EGFR-mutated NSCLC patients treated with first-line TKI who experienced RECIST progression between June 2010 and July 2012. Among the 123 patients included (67?±?12.7 years, women: 69 %, non smokers: 68 %, PS 0–1: 87 %), 40.6 % continued TKI therapy after RECIST progression. There was no difference between the patients who did and did not continue TKI therapy with respect to progression-free survival (PFS1: 10.5 versus 9.5 months, p?=?0.054). Progressions were significantly less symptomatic in the TKI continuation group than in the discontinuation group (18 % vs. 37 %, p?=?0.001), >1 one metastatic site (HR 1.96, 95 %CI: 1.06-3.61, p?=?0.02) at diagnosis, and a trend towards a higher risk of death in cases of TKI discontinuation after progression (HR 1.62, 95 %CI: 0.98-2.67, p?=?0.00001) and >1 metastatic site (HR 2.54, 95 %CI: 1.24-5.21, 相似文献   

Activity of the EGFR-HER2 Dual Inhibitor Afatinib in EGFR-Mutant Lung Cancer Patients With Acquired Resistance to Reversible EGFR Tyrosine Kinase Inhibitors

BackgroundThe purpose of this study was to evaluate the efficacy of afatinib in EGFR-mutant metastatic NSCLC patients with acquired resistance to erlotinib or gefitinib.Materials and MethodsWe retrospectively analyzed the outcome of patients with EGFR-mutant advanced NSCLC treated with afatinib after failure of chemotherapy and EGFR TKIs.ResultsA total of 96 individuals were included in the study. According to EGFR status, most patients (n = 63; 65.6%) harbored a deletion in exon 19, and de novo T790M mutation was detected in 2 cases (T790M and exon 19). Twenty-four (25%) patients underwent repeated biopsy immediately before starting afatinib and secondary T790M was detected in 8 (33%) samples. Among the 86 patients evaluable for efficacy, response rate was 11.6%, with a median progression free-survival (PFS) and overall survival (OS) of 3.9 and 7.3 months, respectively. No significant difference in PFS and OS was observed according to type of last therapy received before afatinib, type of EGFR mutation or adherence to Jackman criteria, and patients benefiting from afatinib therapy had longer PFS and OS (P < .001). Outcome results for repeated biopsy patients were similar to the whole population, with no evidence of response in T790M-positive patients. All patients were evaluable for toxicity, and 81% experienced an AE of any grade, with grade 3 to 4 AEs, mainly diarrhea and skin toxicity, occurring in 19 (20%) patients.ConclusionOur results showed that afatinib has only modest efficacy in a real life population of EGFR mutant NSCLC patients with acquired resistance to erlotinib or gefitinib.     

Survival of Asian Females With Advanced Lung Cancer in the Era of Tyrosine Kinase Inhibitor Therapy

Introduction

We examined the effect of access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on survival for Asian female (AF) EGFR mutation-enriched patients with advanced lung adenocarcinoma.

局部晚期非小细胞肺癌同步放化疗并序贯化疗与单纯序贯放化疗的对比研究

目的 观察局部晚期非小细胞肺癌（NSCLC）接受调强放疗（IMRT）联合同步吉西他滨和卡铂方案（GC）化疗与序贯放化疗的近、远期疗效和不良反应。方法 回顾性分析不能进行手术治疗和拒绝手术治疗的局部晚期NSCLC患者65例,其中同步放化疗并序贯化疗组给予IMRT同步联合GC治疗者32例,单纯序贯放化疗组为33例给予IMRT后序贯GC治疗。通过统计分析比较两组之间的近期有效率、远期生存率和不良反应。结果 两组均完成治疗,随访率100%,同步放化疗并序贯化疗组近期有效率为75%,单纯序贯放化疗组为66.7% ,两组比较差异有统计学意义（P＜0.05）。两组1、3年生存率相比较,同步放化疗并序贯化疗组为68. 2% 、20. 5% ;单纯序贯放化疗组为 50. 1% 、11.3%;同步放化疗并序贯化疗组明显优于单纯序贯放化疗组（P＜0.05）。两组不良反应情况对比,差异无统计学意义（P＞0.05）。结论 IMRT同步联合GC方案并序贯化疗治疗局部晚期NSCLC,可以提高患者的远期生存率且不良反应可耐受。     

A Randomized Phase III Study Comparing Carboplatin With Nab-Paclitaxel Versus Docetaxel for Elderly Patients With Squamous-Cell Lung Cancer: Study Protocol

Background

Treatment with carboplatin (CBDCA) with weekly paclitaxel (PTX) has shown survival benefits compared with vinorelbine or gemcitabine in elderly patients with non-small-cell carcinoma (NSCLC). Docetaxel (DOC), however, remains a standard treatment in NSCLC. The 130-nm albumin-bound formulation of PTX (nab-PTX) has shown activity in NSCLC. Treatment with CBDCA with weekly nab-PTX showed significantly higher efficacy than CBDCA with PTX in patients with squamous histology and significantly increased overall survival (OS) in patients aged 70 years and older.

培美曲塞联合奥沙利铂化疗对晚期非小细胞肺癌的临床疗效

目的 探讨培美曲塞联合奥沙利铂化疗对晚期非小细胞肺癌的临床疗效.方法 选取100例晚期非小细胞肺癌的患者,按照随机数表法将100例患者分为对照组与观察组.对照组采用常规化疗方法,即应用吉西他滨联合奥沙利铂化疗.观察组采用培美曲塞联合奥沙利铂化疗.观察比较两组患者临床疗效,生活质量,血清糖类抗原(CA) 125及癌胚抗原(CEA)水平变化,不良反应.结果 观察组临床有效率为40.0％,对照组为34.0％,两组有效率比较无统计学意义(P＞0.05),观察组临床控制率为80.0％,对照组临床控制率为74.0％,无统计学意义(P＞0.05).观察组治疗后体质量为(71.9±5.1)kg,明显高于对照组患者的(66.9±3.1)kg,差异明显,具有统计学意义(P＜0.05).观察组在治疗后卡氏评分为(86.4±5.7)分,明显高于对照组患者的(75.4±4.7)分,差异明显,具有统计学意义(P＜0.05).观察组在治疗后血清CEA含量为(10.2±6.1)μg·L-1,明显低于对照组患者的(19.3±5.9)μg·L-1,差异明显,具有统计学意义(P＜0.05).观察组在治疗后CA125含量为(38.8 ±3.2)U·mL-1,明显低于对照组患者的(49.3±2.1)U·mL-1,差异明显,具有统计学意义(P＜0.05).两组患者不良反应比较,未见统计学差异(P＞0.05).结论 培美曲塞联合奥沙利铂化疗对患者生活质量的恢复具有显著作用.     

培美曲塞及吉西他滨分别联合顺铂治疗初治晚期非小细胞肺癌安全性和有效性的随机对照研究

背景与目的由于不同个体间肿瘤细胞的生物学特性差异以及现有药物在疗效和不良反应方面仍存在的一定缺陷,故本研究旨在比较培美曲塞及吉西他滨分别联合顺铂治疗初治晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床疗效及毒副作用。方法 251例患者被随机分为培美曲塞联合顺铂组(PP组)127例和吉西他滨联合顺铂组(GP组)124例。PP组:培美曲塞500mg/m2,d1,顺铂75mg/m2,d1。GP组:吉西他滨1,000mg/m2,d1,8,顺铂75mg/m2,d1。两组治疗周期均为每3周1次。此外,两组均合并给药叶酸、VitB12和地塞米松。结果 PP组和GP组患者的总有效率分别为25.20%和17.74%,其中非鳞癌患者总有效率分别为27.62%和16.00%。两组肿瘤进展时间分别为6.5个月和5.6个月,中位生存期分别为16.9个月和17.0个月,1年生存率分别为59.62%和65.87%,2年生存率分别为27.28%和27.93%。PP组非鳞癌的总有效率明显高于GP组,结果具有统计学意义。但两组总缓解率、肿瘤进展时间、中位生存期、1年及2年生存率均无明显性差异。从不良反应来看,PP组的白细胞减少、血小板降低、血红蛋白降低、脱发等不良反应明显低于GP组,结果具有统计学意义。结论培美曲塞联合顺铂治疗晚期非小细胞肺癌与吉西他滨联合顺铂疗效相当,但副作用明显减少。总之,培美曲塞联用顺铂可以作为安全有效的药物对初治的非小细胞肺癌进行临床一线治疗。     

紫杉醇脂质体诱导加同期放化疗与序贯放化疗治疗局部晚期非小细胞肺癌的随机对照研究

背景与目的序贯放化疗及同期放化疗在局部晚期肺癌治疗中得以广泛研究,而诱导加同期放化疗的研究尚少。紫杉醇脂质体副作用少,可使诱导加同期放化疗更顺利地实施。本文旨在比较紫杉醇脂质体加顺铂(TP方案)诱导加同期放化疗和序贯放化疗治疗局部晚期非小细胞肺癌(non-small celllung cancer,NSCLC)的疗效及毒副作用。方法我院60例局部晚期NSCLC患者随机分为诱导加同期放化疗组(A组)和序贯放化疗组(B组)。A组:诱导化疗2个-3个周期后行同期放化疗,放疗的第1天及第22天予TP方案化疗(紫杉醇脂质体135mg/m2-175mg/m2,d1;顺铂70mg/m2-80mg/m2,d2),期间持续放疗。B组:化疗方案同前,化疗4个-6个周期后,行放疗。两组放疗方式均为三维适形放疗,总剂量为56Gy-70Gy。观察和比较两组的疗效和毒副作用。结果 A组、B组总有效率分别为80.3%和60%,组间有统计学差异(P=0.042);1年生存率分别为71.4%和53.2%,组间无统计学差异(P=0.18);骨髓抑制发生率分别为90%和73.3%,组间无统计学差异(P=0.09);放射性食管炎发生率分别为50%和36.7%,组间无统计学差异(P=0.147);肺纤维化发生率分别为30%和20%,组间无统计学差异(P=0.276)。结论在晚期NSCLC的局部治疗中,TP方案诱导加同期放化疗较序贯放化疗的近期疗效好,但毒副反应无明显区别。     

直线加速器联合γ刀放疗同步DP方案化疗治疗局部晚期非小细胞肺癌的临床研究

目的观察直线加速器联合γ刀放疗同步DP方案化疗治疗局部晚期非小细胞肺癌(NSCLC)的近期疗效和不良反应。方法96例局部晚期NSCLC患者随机分为A、B、C三组。A组患者同时接受DP方案化疗及肺内原发灶和阳性淋巴结放疗,6MV X线,50Gy/25F,之后给予γ刀加量20Gy/4F;化疗共4周期。B组患者同时接受DP方案化疗及肺内原发灶和阳性淋巴结放疗,6MV X线,60～66 Gy/30～33F;化疗共4周期。C组患者先接受DP方案化疗2周期后,再给予6MV X线放疗肺内原发灶和阳性淋巴结60～66Gy/30～33F,之后再行DP方案化疗2周期。结果90例患者按计划完成了治疗。A、B、C三组总有效率分别为87.1%、86.7%和62.1%,A、B两组总有效率相当,均高于C组(PAB=1.000,PAC=0.025,PBC=0.030)。三组患者1年总生存率分别为77.4%、73.3%和72.4%,三组相比差异均无统计学意义(PAB=0.711,PAC=0.655,PBC=0.937)。治疗的不良反应主要为急性放射性食管炎、放射性肺炎、骨髓抑制和消化道反应。2级及以上放射性肺炎的发生率分别为323%,60.0% 和20.7%,B组高于A组和C组,A、C两组相当(PAB= 0.030,PAC=0311, PBC=0002); 2级及以上骨髓抑制的发生率分别为61.3%,66.7%和31.0%,A、B两组相当,均高于C组(PAB=0.662,PAC=0.019,PBC=0.006);放射性食管炎和消化道反应三组相比差异无统计学意义。结论直线加速器联合γ刀同步DP方案化疗治疗局部晚期NSCLC的近期疗效好,不良反应经对症处理后患者能耐受,但其远期疗效和并发症有待进一步观察。     

紫杉醇联合铂类药物治疗晚期非小细胞肺癌的临床研究

目的评价紫杉醇联合铂类药物对晚期非小细胞肺癌的客观疗效及毒副作用。方法经病理组织学证实的晚期非小细胞肺癌59例,采用紫杉醇135mg/m^2,静脉滴注,第1天,顺铂80mg/m^2,分3天给药,第2～4天,或卡铂350mg/m^2,静脉滴注,第2天,2l天为1个周期,2个周期以上评价疗效及毒副作用。结果全组PR24例,SD23例,PD12例,总有效率为40.7%。主要毒副作用为恶心、呕吐、骨髓抑制、关节肌肉痛等。大部分为Ⅰ～Ⅱ度不良反应,患者耐受良好。结论紫杉醇联合铂类方案是1种对晚期非小细胞肺癌有效的治疗方案,毒副作用轻,值得临床进一步研究应用。     

表皮生长因子受体酪氨酸激酶抑制剂在晚期非小细胞肺癌一线治疗中的应用

背景与目的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)已广泛用于晚期非小细胞肺癌的二、三线治疗,但其在一线治疗中的作用尚未明确。本文旨在探讨EGFR-TKI一线治疗晚期非小细胞肺癌的疗效及安全性。方法对77例一线使用EGFR-TKI吉非替尼或厄洛替尼治疗的晚期非小细胞肺癌患者的临床特征、治疗效果及生存时间进行回顾性分析,并对药物副作用与安全性进行评估。结果EGFR-TKI一线治疗总有效率为33.8%,疾病控制率为68.8%。中位无进展生存时间为6.0个月,中位生存时间为8.9个月,1年生存率为61.4%。统计学分析显示:病理类型、PS评分、皮疹情况、吸烟史、EGFR突变和血清CEA变化与疗效相关;病理类型和皮疹为影响生存的独立因素。药物不良反应主要表现为皮疹和轻度腹泻。患者服用EGFR-TKI后,疾病相关症状得到缓解,生活质量明显改善。结论EGFR-TKI一线治疗晚期非小细胞肺癌安全有效。     

Axitinib or Bevacizumab Plus FOLFIRI or Modified FOLFOX-6 After Failure of First-Line Therapy for Metastatic Colorectal Cancer: A Randomized Phase II Study

ObjectiveAxitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, shows activity in multiple tumor types, including those refractory to previous antiangiogenic therapy. This randomized, multicenter, parallel-group, open-label phase II trial compared axitinib with bevacizumab each in combination with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) for second-line treatment of metastatic colorectal cancer.MethodsPatients were randomized 1:1 to axitinib 5 mg twice daily or bevacizumab 5 mg/kg every 2 weeks plus modified FOLFOX-6 (if previously treated with irinotecan) or FOLFIRI (if previously treated with oxaliplatin) and were stratified by performance status and prior bevacizumab therapy. Primary endpoint was progression-free survival.ResultsIn 171 patients, progression-free survival was 7.6 months with axitinib/FOLFOX vs. 6.4 months with bevacizumab/FOLFOX (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.55-1.96; 1-sided P = .55) and 5.7 months with axitinib/FOLFIRI vs. 6.9 months with bevacizumab/FOLFIRI (HR, 1.27; 95% CI, 0.77-2.11; 1-sided P = .83). Overall survival was 17.1 vs. 14.1 months with axitinib/FOLFOX and bevacizumab/FOLFOX (HR, 0.69; 95% CI, 0.37-1.27; 1-sided P = .12) and 12.9 vs. 15.7 months with axitinib/FOLFIRI and bevacizumab/FOLFIRI (HR, 1.36; 95% CI, 0.82-2.24; 1-sided P = .88). More grade ≥ 3 adverse events (eg, diarrhea, fatigue, decreased appetite) and treatment discontinuations due to adverse events occurred with axitinib.ConclusionsCompared with bevacizumab, axitinib did not improve outcomes when added to second-line chemotherapy for metastatic colorectal cancer. With current dosing regimens, axitinib plus FOLFOX or FOLFIRI seems to be less well tolerated than bevacizumab-based regimens.