培美曲塞二钠与多西紫杉醇单药治疗晚期非小细胞肺癌的对比研究

目的:比较培美曲塞二钠和多西紫杉醇对一线化疗失败的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的疗效与不良反应。方法:84例一线化疗失败或不能耐受的晚期NSCLC患者随机分为培美曲塞二钠组(44例)和多西紫杉醇组(40例),分别接受培美曲塞二钠500 mg/m2治疗和多西紫杉醇75 mg/m2治疗。入选患者均接受2~6个周期化疗。结果:所有患者参与评价,单用培美曲塞二钠组及单用多西紫杉醇组的有效率分别是13.6%(6/44)和10.0%(4/40);疾病控制率分别是54.5%(24/44)和55.0%(22/40),两组的差异均无统计学意义,χ2=0.002,P值分别为0.741和0.967。单用培美曲塞二钠组和多西紫杉醇组患者的中位生存时间分别为8.2和8.1个月,1年生存率分别为27.3%和25.0%,两组的差异均无统计学意义,P值分别为0.258和0.580。两组的不良反应均为骨髓抑制、恶心、呕吐、乏力及脱发。培美曲塞二钠组发生中性粒细胞减少的概率明显低于多西紫杉醇组,Ⅰ~Ⅱ度分别为31.8%(14/44)和65.0%(26/40),χ2=9.249,P=0.002;Ⅲ~Ⅳ度分别为4.5%(2/44)和30.0%(12/40),χ2=9.775,P=0.002。结论:对于一线化疗失败或不能耐受的晚期NSCLC患者,分别使用培美曲塞二钠和多西紫杉醇进行化疗,疗效相似,但使用培美曲塞二钠化疗的不良反应更低,值得临床推广使用。     

培美曲塞治疗19例复发性晚期非小细胞肺癌

背景与目的：晚期复发的非小细胞肺癌治疗效果差,可选择的药物不多。本研究探讨培美曲塞单药或联合顺铂/卡铂治疗晚期复发性非小细胞肺癌（NSCLC）的疗效以及不良反应。方法：经病理学或细胞学确诊的复发性晚期NSCLC患者19例,其中男性9例,女性10例,中位年龄48岁,KPS评分≥70。单药治疗：培美曲塞500mg/m^2,第1天静脉滴注每3周重复;联合治疗：培美曲塞500 mg/m^2第1天＋顺铂60 mg/m^2第2天静脉滴注每3周重复;或培美曲塞500 mg/m^2第1天＋卡铂300 mg/m^2第2天静脉滴注每3周重复。至少2周期以上可评价疗效及不良反应。结果：19例中16例可评价疗效,全组无CR/PR病例,MR 2例,SD 10例,PD 4例,疾病控制率75%（12/16）。中位生存时间9个月,1年生存率为31%（5/16）。主要不良反应为粒细胞下降、贫血和胃肠道反应。结论：培美曲塞单药或联合铂类治疗晚期复发NSCLC疗效确切,不良反应发生率低,耐受性较好。     

Rationale and Design of MILES-3 and MILES-4 Studies: Two Randomized Phase 3 Trials Comparing Single-Agent Chemotherapy Versus Cisplatin-Based Doublets in Elderly Patients With Advanced Non–Small-Cell Lung Cancer

BackgroundPlatinum-based chemotherapy is the cornerstone of treatment of advanced non-small-cell lung cancer (NSCLC) patients, but the efficacy of adding cisplatin to single-agent chemotherapy remains to be demonstrated in prospective phase III trials dedicated to elderly patients. Furthermore, the superiority of cisplatin/pemetrexed over cisplatin/gemcitabine in non-squamous NSCLC has not been confirmed prospectively. We present the rationale and design of two open-label, multicenter, randomized phase III trials for elderly patients with advanced NSCLC∶ Multicenter Italian Lung cancer in the Elderly Study (MILES)-3 and MILES-4. The aim is to evaluate the efficacy of adding cisplatin to single-agent chemotherapy (both trials) and the efficacy of pemetrexed versus gemcitabine in non-squamous tumors (MILES-4).Patients and MethodsBoth trials are dedicated to first-line therapy of patients older than 70 years with advanced NSCLC, ECOG performance status 0-1. In the MILES-3 trial, patients are randomized in a 1∶1 ratio to gemcitabine or cisplatin/gemcitabine. In the MILES-4 study patients with non-squamous histology are randomized, in a factorial design with 1∶1∶1∶1 ratio, to four arms: gemcitabine (A), cisplatin/gemcitabine (B), pemetrexed (C), cisplatin/pemetrexed (D). Two comparisons are planned∶ A+C vs B+D to test the role of cisplatin; A+B vs C+D to test the role of pemetrexed. Primary endpoint of both trials is overall survival. Secondary and exploratory endpoints include progression-free survival, response rate, toxicity, and quality of life.ConclusionsMILES-3 and MILES-4 results will add important evidence about the role of cisplatin-based doublets and pemetrexed in the first-line therapy of elderly patients with advanced NSCLC.     

吉非替尼联合培美曲塞和顺铂治疗晚期非小细胞肺癌的安全性和有效性

目的:比较单用培美曲塞/顺铂化疗或吉非替尼联合培美曲塞/顺铂化疗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,为临床应用提供参考。方法:选择标准一线化疗后复发的晚期NSCLC患者112例,其中联合治疗组52例接受培美曲塞/顺铂及吉非替尼治疗,化疗组60例仅采用培美曲塞和顺铂化疗,评价两组患者的临床疗效及不良反应。结果:联合组客观有效率（objective response rate,ORR）为36.5%,高于化疗组的18.3%（P=0.030）;两组疾病控制率（disease control rate,DCR）分别为71.2%和55.0%（P=0.035）;两组患者的中位无进展生存期（progression free survival,PFS）分别为8.7个月和6.7个月,差别有统计学意义（P=0.047）,但两组患者的中位总生存期（overall survival,OS）差别无统计学意义（P=0.265）。与治疗前相比,两组患者的肿瘤标志物均明显下降,但联合组的CEA和CYFRA21-1水平比化疗组更低（P<0.05）。联合组皮疹和腹泻的发生率高于化疗组（P<0.05）,两组之间其它不良反应的发生率无明显差别（P>0.05）。结论:晚期NSCLC患者一线化疗失败后,采用培美曲塞/顺铂化疗联合吉非替尼靶向治疗较单用化疗显示出更高的ORR和中位PFS,且不良反应可以耐受,值得临床推广运用。     

培美曲塞联合长春瑞滨治疗老年中晚期非小细胞肺癌的临床观察

目的研究培美曲塞（Alimta）联合长春瑞滨（NVB）治疗老年中晚期非小细胞肺癌（NSCLC）的疗效及不良反应。方法入组33例老年中晚期非小细胞肺癌初治或复治患者,培美曲塞500mg/m2,静脉滴注10min以上,第1天;长春瑞滨25mg/m2,加生理盐水40ml静脉推注,第1、8天,每3周为一周期,2个周期后评价疗效。结果 33例患者中完全缓解（CR）1例,部分缓解（PR）17例,稳定（SD）9例,进展（PD）6例,有效率（CR＋PR）54.5%。结论培美曲塞（Pemetrexed Alim-ta）联合长春瑞滨（Navelbine,NVB）治疗老年中晚期非小细胞肺癌（NSCLC）的疗效较好,副作用可耐受,可作为治疗老年中晚期非小细胞肺癌（NSCLC）的一线或二线化疗方案。     

培美曲塞联合顺铂一线治疗晚期非小细胞肺癌的临床观察

目的 评价培美曲塞联合顺铂一线治疗晚期非小细胞肺癌( NSCLC)的临床疗效和毒副反应.方法 48例初治晚期NSCLC接受培美曲塞联合顺铂化疗,接受2个周期化疗后评价临床疗效和毒副反应.结果 48例中,PR 13例,SD 15例,PD 20例,有效率27.08％,临床获益率58.33％.主要毒副反应为骨髓抑制、胃肠道反...     

Pemetrexed

Pemetrexed (ALIMTA, LY231514) is a novel, multi targeted antifolate chemotherapy agent that is active in various tumors including mesothelioma, NSCLC, breast, colon and bladder carcinoma. Pemetrexed inhibits several enzymes in the folate pathway including thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed is approved in the United States and a number of European Union countries for use in the treatment of mesothelioma, and the second-line treatment of advanced NSCLC. However, in Japan, pemetrexed was approved for use only in combination with cisplatin in the treatment of mesothelioma in January 2007. This approval was granted on the basis of a phase III trial of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. Treatment with pemetrexed plus cisplatin and vitamin supplementation, resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone. In addition, in a phase III trial of pemetrexed versus docetaxel in patients with NSCLC previously treated with chemotherapy, treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects including grade 3 or 4 neutropenia , neutropenic fever, and alopecia, compared with docetaxel. Therefore, pemetrexed should be considered a standard treatment option for second-line NSCLC in US and most of EU. Addition of folic acid and vitamin B12 significantly reduced the toxicity of pemetrexed, especially hematologic toxicity and gastrointestinal toxicity. Pemetrexed is the expected agent for use in high risk patients, especially elderly or poor performance status patients.     

Apatinib Plus Chemotherapy Shows Clinical Activity in Advanced NSCLC: A Retrospective Study

Apatinib is an oral TKI with antiangiogenic properties, and it is currently approved for the treatment of advanced gastric cancer in China. This agent has also been tested in other human solid tumors, including non-small cell lung cancer (NSCLC). Since the combination of chemotherapy and an antiangiogenic agent has been shown to be a feasible strategy in NSCLC, it is conceivable that a similar approach combining apatinib with chemotherapy may yield clinical activity. With this in mind, we investigated the efficiency of apatinib in combination with pemetrexed or docetaxel in advanced NSCLC. We treated a total of 20 patients with metastatic NSCLC adenocarcinoma with apatinib in combination with either pemetrexed or docetaxel from January 2016 to March 2017. The performance status of these patients was 0 or 1. All of these patients had been previously treated with two or more lines of treatment and had experienced disease progression prior to study enrollment. The overall objective response rate (ORR) was 30%, with 6 patients who had partial response (PR), 10 patients who had stable disease (SD), and 4 patients who had progressive disease (PD). The main adverse events were skin rash, hypertension, palmar–plantar erythrodysesthesia syndrome, diarrhea, and fatigue. Nearly 30% of patients required interruption of treatment as a result of toxicity. Our study demonstrated that apatinib combined with systemic cytotoxic chemotherapy has clinical efficacy in patients with disease-refractory metastatic NSCLC and provides evidence for further studies investigating apatinib-based combination regimens.     

培美曲塞单药与联合铂类药物二线治疗晚期非小细胞肺癌的临床观察

目的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)一线化疗有效率仅30%～40%。复发或初治无效患者的治疗,需引入新的药物及治疗方法。本试验观察培美曲塞单药或联合铂类二线治疗复发晚期NSCLC的疗效及毒副反应。方法回顾性分析经病理学或细胞学确诊的复发或转移性NSCLC腺癌患者共66例。其中应用培美曲塞单药治疗32例,培美曲塞联合铂类药物治疗34例。患者均接受2～4个周期该方案治疗。结果 66例患者均可评价疗效及毒副反应,CR 0例,PR 17例,SD 20例,PD 29例。其中单药组CR 0例、PR 7例、SD 10例、PD 15例,联合组CR 0例、PR 10例、SD 10例、PD 14例。单药与联合组的DCR(CR+PR+SD)、1年生存率、中位PFS、中位OS分别为53.1%和58.8%(P=0.64)、26.4%和35.3%(P=0.17)、2.5个月和2.7个月(P=0.09)、8.4个月和10.1个月(P=0.39),均无统计学差异。两组的主要不良反应均为白细胞减少、贫血和消化道反应。但老年组(≥65岁)亚组分析结果显示单药组的血液学毒性、消化道反应及皮疹的发生率均显著低于联合组。结论培美曲塞单药或联合铂类药物方案用于复发晚期NSCLC腺癌的二线治疗疗效和毒副反应均无显著性差异。培美曲塞单药对比联合铂类药物对于老年患者安全性更高。     

Advances in the treatment of second-line non-small-cell lung cancer

Treatment with third-generation chemotherapy agents improves survival and quality of life of patients with non-small-cell lung cancer (NSCLC). Despite these favorable outcomes, most patients receiving front-line therapy experience disease progression. The availability of many new novel agents with activity in NSCLC has prompted investigators to explore second-line chemotherapy options. For many years, docetaxel was the only approved agent for the second-line treatment of NSCLC. More recently, the multi-targeted antifolate pemetrexed has demonstrated activity in patients previously treated with chemotherapy with locally advanced or metastatic NSCLC. The findings of a phase III trial comparing pemetrexed to docetaxel led to the regulatory approval of pemetrexed as monotherapy for the second-line treatment of NSCLC. Several other novel therapies, including molecular targeting agents such as erlotinib, are under development in clinical trials in patients with NSCLC. One of these trials has subsequently led to the approval of erlotinib as second- or third-line therapy in advanced NSCLC.     

复治晚期非小细胞肺癌EGFR-TKI治疗失败后培美曲塞与多西他赛挽救性化疗的疗效比较

目的 比较复治晚期非小细胞肺癌（NSCLC）表皮生长因子受体 酪氨酸激酶抑制剂（EGFR TKI）治疗失败后用培美曲塞或多西他赛挽救性化疗的疗效及毒副反应。方法120例复治晚期NSCLC患者于EGFR-TKI治疗失败后分别接受培美曲塞（500mg／m2,d1）或多西他赛（75mg／m2,d1）的挽救性化疗,均21天为1周期。记录并比较两者的疗效和预后。结果培美曲塞组和多西他赛组的有效率（RR）分别为13.4％和5.3％（P=0.307）,疾病控制率（DCR）分别为58.5％和42.1％（P=0.093）,中位无进展生存期（PFS）分别为2.83个月和2.10个月（P=0.862）,中位总生存期（OS）分别为8.40个月和9.10个月（P=0.527）。EGFR-TKI治疗有效和挽救性化疗前行为状态评分（PS）≤1者的中位PFS较长。培美曲塞组1～4级中性粒细胞减少的发生率低于多西他赛组,分别为41.5％和65.8％（P=0.013）。在非血液学毒性方面两组差异均无统计学意义（P＞0.05）。结论 复治晚期NSCLC TKI治疗失败后用培美曲塞或多西他赛挽救性化疗,部分患者仍可以获益,两组疗效相当,且大部分患者能够耐受化疗的毒副反应。对于EGFR-TKI治疗有效、挽救性化疗前PS评分较好的患者,有可能从挽救性化疗中获益更大。     

吉非替尼对比培美曲塞二线治疗晚期非小细胞肺癌的临床研究

目的：观察吉非替尼与培美曲塞二线治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）情况,比较二者对晚期NSCLC患者的治疗效果、安全性的影响。方法将一线化疗治疗失败后的105例晚期NSCLC患者,随机分为吉非替尼组和培美曲塞组,分别接受吉非替尼与培美曲塞二线治疗,比较两组患者的治疗效果和安全性。结果近期疗效比较结果显示,吉非替尼组和培美曲塞组客观有效率（ORR）分别为24.0%和29.1%（P=0.987）,疾病控制率（DCR）分别为64.0%和70.9%（P=0.776）;吉非替尼组和培美曲塞组中位无进展生存时间（PFS）分别为5.2个月和4.1个月（P=0.026）,中位总生存期（OS）分别为7.9个月和6.7个月（P=0.031）,吉非替尼组PFS和OS均优于培美曲塞组。吉非替尼组的不良反应主要为非血液学毒性,培美曲塞组的主要不良反应为血液学毒性。结论吉非替尼及培美曲塞均可用于晚期NSCLC患者的二线治疗,疗效相当,但二者的不良反应各异,可根据患者的个体差异择优选用。     

Chemotherapy in non-small cell lung cancer：opportunities for advancement

Locally advanced non-small cell lung cancer (NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is significant interest in finding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical Oncology entitled“PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer”, compared two different chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received con-solidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no difference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not offer a clinical advantage over standard cisplatin plus etopo-side. There are some subpopulations who might still benefit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.     

Multi-targeted-Enzyminhibition in der Tumortherapie

Pemetrexed is a newly developed therapeutic agent which inhibits several key enzymes in the folate metabolic pathway. In phase I trials, this novel multitargeted antifolate showed a broad antitumor activity as a single agent and in combination chemotherapy. Based on these findings, phase III studies have been conducted including patients with malignant pleural mesothelioma (MPM), non-small-cell lung cancer (NSCLC), and colorectal cancer. In a recent phase III trial in MPM, the combination of pemetrexed and cisplatin was significantly more efficacious than cisplatin alone. In addition, vitamin supplementation reduced treatment-associated toxicities with no apparent affect on activity. In patients with NSCLC, a phase III trial showed clinically equivalent efficacy of pemetrexed and docetaxel, but pemetrexed was associated with significantly fewer toxicities in second-line therapy. This review summarizes preclinical and clinical data to define the future role of pemetrexed in the treatment of tumor patients.     

AP化疗方案治疗EGFR-TKI一线化疗失败非小细胞肺癌患者的疗效及对预后的影响

目的探讨培美曲塞联合顺铂(AP)化疗方案二线治疗表皮生长因子受体-酪氨酸激酶抑制剂(EGFRTKI)一线治疗失败非小细胞肺癌(NSCLC)患者的疗效及对预后的影响。方法将90例经EGFR-TKI一线化疗失败的NSCLC患者根据随机数字表法分为AP组(培美曲塞联合顺铂)和GP组(吉西他滨联合顺铂),每组45例。比较两组患者化疗近期疗效、不良反应、生活质量及生存情况。结果AP组患者客观缓解率(ORR)与疾病控制率(DCR)均略高于GP组,但差异均无统计学意义(P>0.05)。AP组患者白细胞减少、中性粒细胞减少、血小板下降发生率均低于GP组,差异均有统计学意义(P<0.05)。化疗前,两组患者Karnofsky评分比较,差异均无统计学意义(P>0.05);化疗后,两组患者Karnofsky评分均升高,差异均有统计学意义(P<0.05)。两组生存情况比较,差异无统计学意义(P>0.05)。结论二线AP和GP化疗方案对EGFR-TKI一线治疗失败NSCLC患者近期疗效、生存时间和生活质量影响相似,但AP方案不良反应较少,更为安全。     

Phase II study of pemetrexed as first-line treatment in elderly (≥75) non-squamous non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial 0901

Background

Single-agent chemotherapy with third-generation non-platinum agents, such as docetaxel, vinorelbine, is a standard therapeutic option for elderly patients with non-small-cell lung cancer (NSCLC). Subset analysis of a previous phase III study comparing pemetrexed with docetaxel in the second-line setting showed the superiority of pemetrexed in an elderly (≥70) population in both efficacy and toxicity.

Patients and methods

This was a single-arm phase II study of pemetrexed in elderly (≥75) Japanese patients with advanced non-squamous NSCLC. Patients received four cycles of pemetrexed (500 mg/m²) every 3 weeks. The primary endpoint was the response rate, and secondary endpoints were safety and survival.

Results

Twenty-eight patients were enrolled between January 2010 and April 2012. The median age of the patients was 77 years (range 75–88). All but one patient had adenocarcinoma histology. The median number of chemotherapy cycles administered was 4 (range, 1–12). Seventeen (60 %) patients completed four cycles of chemotherapy. Partial response was achieved in 7 patients (response rate: 25 %) and stable disease in 11 patients (disease control rate: 64 %). Median progression-free survival and overall survival were 3.3 and 17.5 months, respectively. Grade 3/4 neutropenia and thrombocytopenia were observed in 8 patients (29 %) and 2 (7 %), respectively. Non-hematologic toxicities were generally mild, and there were no treatment-related deaths.

Conclusions

Although this study did not meet our primary endpoint, pemetrexed showed favorable antitumor activity with mild toxicity in elderly patients with non-squamous NSCLC. Further investigations of pemetrexed in this population are warranted (UMIN-CTR number, 000002452).     

国产培美曲塞治疗进展性非小细胞肺癌近期疗效分析

目的回顾性分析国产培美曲塞（普来乐）治疗进展性非小细胞肺癌（NSCLC）的近期疗效性和毒副反应。方法 24例经组织学及细胞学证实的晚期进展的NSCLC患者,使用国产培美曲塞单药治疗,500mg/m2,静脉滴入,d1,21d为1个周期,连用2～4个周期,进行疗效及毒副反应评价。结果 24例均可评价疗效,CR0例,PR3例,PD8例,SD13例;有效率（RR）为12.5%（3/24）,疾病控制率（DCR）为45.8%（11/24）。毒副反应主要表现为轻到中度胃肠道反应和骨髓抑制。结论国产培美曲塞治疗晚期进展性NSCLC具有较好的疗效且毒副反应轻。     

培美曲塞与吉非替尼二线治疗晚期非小细胞肺癌的临床对比分析

目的探讨培美曲塞与吉非替尼单药治疗一线化疗失败的晚期非小细胞肺癌（NSCLC）的疗效及安全性,为NSCLC的二线临床用药提供一定的参考依据。方法将符合人组标准的83例患者随机分成培美曲塞组（41例）和吉非替尼组（42例）进行治疗观察,两组患者在性别、年龄、病理类型、分期,吸烟史等方面大致平衡。评价两组患者的疗效、无进展生存时间（PFS）、中位生存时间（MST）和不良反应。结果比较两组患者的中位PFS、中位OS、肿瘤分期、一线接受化疗方案个数等指标,两组差异均无统计学意义（P〉0．05）,但吉非替尼组的血液学毒性明显低于培美曲塞组（P〈0．05）,症状改善及生活质量改善优于培美曲塞组（P〈0．05）。结论在标准一线化疗失败的晚期NSCLC患者中,培美曲塞和吉非替尼单药二线治疗晚期非小细胞肺癌效率相近,但吉非替尼不良反应轻微,对症状和生活质量的改善率更高。     

培美曲塞联合顺铂治疗复发性晚期非小细胞肺癌45例

目的 探讨培美曲塞联合顺铂治疗复发性晚期非小细胞肺癌(NSCLC)的疗效及毒副反应.方法45例经病理学确诊的复发性晚期NSCLC接受化疗:培美曲塞500 mg/m2,d1,静脉滴注;顺铂30 mg/m2,d1～3,静脉滴注,21 d为1个周期.2个周期后评价疗效及毒副反应.结果45例中,CR 0例、PR 23例、NC ...     

The SATURN trial: the value of maintenance erlotinib in patients with non-small-cell lung cancer

The first-line treatment of advanced non-small-cell lung cancer (NSCLC) generally consists of a maximum of six cycles of platinum-based doublet chemotherapy followed by surveillance for disease progression. Recently, the strategy of starting second-line treatment immediately following the completion of chemotherapy, known as 'maintenance' chemotherapy, has been investigated. The use of maintenance pemetrexed improves both progression-free and overall survival, while the use of maintenance docetaxel did not significantly improve overall survival. The Sequential Tarceva in Unresectable NSCLC (SATURN) study investigated the use of maintenance erlotinib following the completion of first-line chemotherapy. It demonstrated a significant improvement in overall survival from 11.1 months in the placebo group to 12.3 months in patients receiving maintenance erlotinib, with the important caveat that only 21% of patients in the placebo group ever received erlotinib. A subset of patients whose tumors had EGF receptor mutations had a higher magnitude of benefit from maintenance treatment. Therefore, maintenance erlotinib should be considered in the treatment of patients with NSCLC.