Comparison of treatment costs of grade 3/4 adverse events associated with erlotinib or pemetrexed maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) in Germany, France, Italy, and Spain

Objective of this indirect economic comparison was to estimate and compare management costs of grade 3/4 adverse events (AEs) reported for first-line erlotinib or pemetrexed maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC). The economic analysis was performed for Germany, France, Italy and Spain.Types and incidences of reported grade 3/4 AEs observed with erlotinib or pemetrexed maintenance therapy were retrieved from two recently published placebo-controlled trials. Country-specific estimates on standard treatment algorithms and incremental medical resource utilization associated with each of the reported grade 3/4 AEs have been obtained from clinical oncologists practicing in the four countries and co-authoring this article. The resource use items were subsequently assigned country-specific tariffs to estimate total per-patients costs associated with the AE profiles of the two compared maintenance regimens. For the economic analysis a customized economic spreadsheet model was employed.Our comparison shows lower total average per-patient AE management costs for erlotinib than for pemetrexed maintenance therapy in all four studied countries. Total estimated cost savings per patient in favour of erlotinib amount to € 121, € 237, € 106, and € 119 for Germany, France, Italy and Spain, respectively. These AE cost savings for erlotinib when compared to pemetrexed represent a decrease by 80%, 71%, 94%, and 82%, respectively. The study also discovered considerable differences in AE management costs across countries which are primarily due to differences in clinician's estimates of hospitalization referral rates.Erlotinib maintenance therapy in patients with advanced NSCLC causes lower AE management costs than pemetrexed maintenance therapy indicating a potentially superior tolerability profile.     

Costs of bevacizumab and pemetrexed for advanced non-squamous NSCLC in Italy and Germany

The new targeted agent bevacizumab in combination with cisplatin and gemcitabine, and a third-generation chemotherapy pemetrexed in combination with cisplatin, have been approved as first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC). An indirect comparison between bevacizumab plus cisplatin and gemcitabine and pemetrexed plus cisplatin showed that bevacizumab (plus cisplatin and gemcitabine) achieved a favourable hazard ratio in terms of progression-free survival among patients with advanced NSCLC. This analysis aimed to compare the monthly cost of these treatments for advanced non-squamous NSCLC in Italy and Germany.The comparison used country specific cost data and adopted the payer perspective in Italy and Germany.The monthly cost of bevacizumab, including administration cost, as a single agent was €1,509 and €2,564 less than pemetrexed in Italy and Germany, respectively. The monthly treatment cost of bevacizumab plus cisplatin and gemcitabine was €1,001 and €446 less than pemetrexed plus gemcitabine in Italy and Germany, respectively.Results indicate that clinical benefits with bevacizumab plus cisplatin and gemcitabine therapy are achieved at a lower monthly cost than pemetrexed plus gemcitabine doublet therapy. Therefore, from a budget perspective, bevacizumab should be considered as a preferred targeted treatment of choice for advanced non-squamous NSCLC.     

Cost-effectiveness analysis of bevacizumab versus pemetrexed for advanced non-squamous NSCLC in Italy

IntroductionThe new targeted agent bevacizumab in combination with cisplatin and gemcitabine (BCG), and a third-generation chemotherapy pemetrexed in combination with cisplatin (PC), are approved as first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC).MethodsAn indirect comparison between BCG and PC showed that the bevacizumab triplet achieved a favourable hazard ratio in terms of progression-free survival among patients with advanced NSCLC. This analysis aimed to compare the detailed costs and benefits of these treatments for advanced non-squamous NSCLC in Italy.ResultsThe monthly cost of single-agent bevacizumab, including administration and supportive care costs, and costs for adverse events as a single agent was €4,007/patient less than pemetrexed over the patient's lifetime. BCG also achieved a mean gain of 0.12 life-years compared with PC over this period. The incremental cost-effectiveness ratio of BCG relative to PC was calculated to be €34,919 per additional life-year gained suggesting that BCG is cost-effective compared with PC as first-line treatment for advanced NSCLC in Italy.ConclusionsIn conclusion, bevacizumab-based therapy can be considered as a cost-effective option when compared to chemotherapy treatments such as pemetrexed for the treatment for advanced non-squamous NSCLC.     

Economic impact of healthcare resource utilisation patterns among patients diagnosed with advanced melanoma in the United Kingdom, Italy, and France: Results from a retrospective, longitudinal survey (MELODY study)

ObjectiveTo describe patterns of healthcare resource utilisation and associated costs for patients with advanced melanoma in the United Kingdom (UK), Italy, and France.MethodsFor patients receiving systemic treatment, or supportive care, data describing hospitalisations, hospice care, and outpatient visits were retrieved retrospectively from advanced disease diagnosis as part of a multicountry observational study. Costs were estimated by multiplying utilisation level by unit cost. In an exploratory analysis, costs were compared between individuals who died within one year of initiating first-line treatment (short-term survivors) and those with ⩾1 year follow-up (long-term survivors).ResultsHospitalisation costs were highest in France (€6262 per-person compared with €3225 in the UK and €2486 in Italy), reflecting higher rates of hospitalisation. In contrast, outpatient costs were highest in the UK (€782 per-person, compared with €115 in France and €72 in Italy), reflecting the highest rate and frequency of outpatient visits and the highest cost per visit. Hospitalisation rates were consistently higher during supportive care compared with systemic therapy. Roughly one-third of patients entered clinical trials and were not included in the analysis. In exploratory analysis, total costs were generally higher for long-term survivors, but monthly per-patient costs were generally lower for long-term survivors, consistent with a hypothesis that resource utilisation and costs do not necessarily increase proportionally with extended survival.ConclusionTotal costs associated with resource utilisation for advanced melanoma patients varied across countries. Overall cost differences were due to differences in frequency and intensity of utilisation patterns and variation in unit costs of health resources.     

Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study

BackgroundErlotinib and pemetrexed are approved single agents for second-line treatment of non-small-cell lung cancer (NSCLC) and, in combination, have shown synergistic antitumor activity in NSCLC cell lines. We investigated the safety, pharmacokinetics and preliminary efficacy of combined erlotinib–pemetrexed in patients with refractory advanced NSCLC.Patients and methodsA nonrandomized, open-label, phase IB study was performed in patients with advanced NSCLC whose disease had progressed on or following first-line chemotherapy with a platinum-containing regimen or for whom the erlotinib–pemetrexed combination was considered appropriate. Patients received i.v. pemetrexed 500–700 mg/m² every 3 weeks and oral erlotinib 100–150 mg/day.ResultsTwenty patients were recruited. The most common adverse events (AEs) were rash, diarrhea and fatigue. Serious AEs occurred in eight patients (three treatment related) and there were eight deaths (none treatment related). Dose-limiting toxic effects were not experienced up to erlotinib 150 mg/day plus pemetrexed 600 mg/m². Concurrent administration did not affect pharmacokinetic parameters. Two patients achieved partial responses and nine had stable disease.ConclusionsErlotinib–pemetrexed combination is well tolerated at doses equal to the licensed single-agent doses (150 mg/day and 500 mg/m², respectively). The good tolerability profile and promising efficacy indicate that this combination warrants further investigation for patients with advanced NSCLC.     

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.     

FDA drug approval summary: erlotinib (Tarceva) tablets

On November 18, 2004, erlotinib (Tarceva); OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com, and Genentech, Inc., South San Francisco, CA, http://www.gene.com) received regular approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Survival of erlotinib-treated patients was superior to that of placebo-treated patients. The median survival duration of erlotinib-treated patients was 6.67 months, compared with 4.70 months for placebo-treated patients. Exploratory univariate analyses showed a larger survival prolongation in two subsets of patients: those who never smoked and those with epidermal growth factor receptor (EGFR)-positive tumors. Patients who never smoked and were EGFR-positive had a large erlotinib survival benefit. Erlotinib was also superior to placebo for progression-free survival and a response rate of 8.9% versus 0.9%. Skin rash and diarrhea were the most common erlotinib adverse events. Severe rash occurred in 8%, and severe diarrhea occurred in 6% of erlotinib-treated patients. In the first-line treatment of NSCLC, two large, controlled, randomized trials showed no benefit from adding erlotinib to doublet, platinum-based chemotherapy. Therefore, erlotinib is not indicated for use in this setting.     

First-line Bevacizumab plus Taxane-based Chemotherapy for Metastatic Breast Cancer: Cost-minimisation Analysis

Aim: To carry out a cost minimisation analysis including a comparison of the costs arising from first-line treatment by bevacizumab plus docetaxel (BD) versus bevacizumab plus paclitaxel (BP) of patients with metastatic breast cancer (mBC). Patient and Methods: All consecutive patients with human epidermal growth receptor 2-negative mBC and treated at Besan?on University hospital between 2006 and 2010 by a first-line therapy containing bevacizumab plus taxane were retrospectively studied. Economic analysis took into account costs related to drugs, hospitalization and healthcare travel. RESULTS: Progression-free survival difference between the two treatments was insignificant (p-value=0.31). BP treatment was associated with a higher mean total cost than that of BD treatment, €53,093±34,395 versus €60,196±48,766, respectively. CONCLUSION: Whereas bevacizumab is recommended for first-line treatment of mBC with paclitaxel-based chemotherapy, our study has shown that BD treatment is the most cost-efficient regimen. It could be an attractive option in France, with a potential cost saving of €24,000,000 per year.     

厄洛替尼与培美曲塞在非小细胞肺癌维持治疗中的疗效比较

目的比较观察厄洛替尼与培美曲塞在晚期非小细胞肺癌（NSCLC）维持治疗中的疗效及毒副反应。方法纳入72例晚期NSCLC患者,一线治疗均给予含铂双药标准一线方案化疗,能顺利完成4周期化疗且病情得到控制者共42例,然后随机均分为2组,分别给予厄洛替尼及培美曲塞维持治疗,比较观察2组的生存情况和毒副反应。结果厄洛替尼组、培美曲塞组的中位无进展生存时间分别为5.8个月、5.5个月,差异无统计学意义（P〉0.05）。厄洛替尼组主要毒副反应为皮疹和腹泻,培美曲塞组主要毒副反应为消化道反应和血液学毒性,2组骨髓抑制、恶心呕吐、皮疹发生率比较差异有统计学意义（P〈0.05）。结论厄洛替尼与培美曲塞作为维持治疗方法治疗晚期NSCLC在延长生存期方面作用相似,但厄洛替尼的毒副反应更轻,患者更易于耐受。     

SEOM clinical guidelines for the treatment of non-small-cell lung cancer: an updated edition

The purpose of this article is to provide updated recommendations for the diagnosis and treatment of patients non-small-cell lung cancer (NSCLC). The staging system for lung cancer has recently been revised by the International Association for Study of Lung Cancer and patients with NSCLC shall now be staged according to the UICC system 7th edition. Recommendations for treatment were based on treatment strategies that improve overall survival. In functionally fit patients with stage I–II disease surgical resection is recommended. Four cycles of adjuvant cisplatin-based chemotherapy is recommended in patients with pathologic stage II-III. For patients with stage IIIA and non-bulky mediastinal lymph node survival was significantly improved with induction chemotherapy plus surgical resection. Patients with unresectable or bulky stage IIIA and those with stage IIIB, should be treated with platinum-based chemotherapy and thoracic radiotherapy. For patients with metastatic disease and performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For elderly patients and those with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with platinum-based chemotherapy, except for patients with certain clinical characteristics. Maintenance therapy with pemetrexed or erlotinib increases survival in patients who did not progress after 4 cycles of a platinum based chemotherapy. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs.     

Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.

PURPOSE: To describe the Food and Drug Administration (FDA) review and approval of erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. EXPERIMENTAL DESIGN: The FDA reviewed raw data in electronic format from a randomized controlled clinical trial comparing erlotinib with placebo in patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. RESULTS: Patients were randomized in a 2:1 ratio (erlotinib, n = 488 and placebo, n = 243). Erlotinib was superior to placebo for survival, progression-free survival, and tumor response rate. Exploratory analyses indicate that epidermal growth factor receptor status may be an important predictor of the erlotinib survival effect. Rash (75% versus 17%) and diarrhea (54% versus 18%) in the erlotnib and placebo group respectively were the most common adverse events. Severe rash occurred in 9% and severe diarrhea in 6% of erlotinib-treated patients and each resulted in study discontinuation in 1% of patients. Dose reductions were required for 10% of patients with rash and 4% of patients with diarrhea. CONCLUSIONS: On November 18, 2004, the FDA granted erlotinib regular approval for treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. The applicant has committed to conduct post-marketing clinical trials to assess further the effect of epidermal growth factor receptor expression, measured with immunohistochemical staining, on erlotinib treatment effect.     

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.     

Second-line treatment of non-small-cell lung cancer: chemotherapy or tyrosine kinase inhibitors?

After first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC), many patients remain candidates for a second-line treatment. Docetaxel, pemetrexed and erlotinib are currently approved in the USA and Europe as second-line therapy for NSCLC, while gefitinib is approved and licensed in Europe, but not in the USA, for EGF receptor-mutated patients in the same setting. Results of the registration trials for these four agents show similar efficacy in terms of objective response rate and survival, but significantly different toxicity and tolerability. Therefore, at the time of failure of first-line treatment, it is crucial to evaluate different clinical factors that could help choose the second-line treatment of metastatic NSCLC, as performance status and comorbidities; new predictive biomarkers will be validated in future trials. Considering the different predictive and prognostic factors, tyrosine kinase inhibitors could be a valid option for second-line treatment of NSCLC.     

Second-line treatment of non-small-cell lung cancer: chemotherapy or tyrosine kinase inhibitors?

After first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC), many patients remain candidates for a second-line treatment. Docetaxel, pemetrexed and erlotinib are currently approved in the USA and Europe as second-line therapy for NSCLC, while gefitinib is approved and licensed in Europe, but not in the USA, for EGF receptor-mutated patients in the same setting. Results of the registration trials for these four agents show similar efficacy in terms of objective response rate and survival, but significantly different toxicity and tolerability. Therefore, at the time of failure of first-line treatment, it is crucial to evaluate different clinical factors that could help choose the second-line treatment of metastatic NSCLC, as performance status and comorbidities; new predictive biomarkers will be validated in future trials. Considering the different predictive and prognostic factors, tyrosine kinase inhibitors could be a valid option for second-line treatment of NSCLC.     

Erhaltungstherapie oder ?treatment holiday�� nach Erstlinientherapie

Maintenance chemotherapy may be a treatment option in patients with advanced non-small-cell lung cancer (NSCLC). First-line therapy can be continued with the ongoing administration of one of the first-line drugs or a switch to one of the second-line drugs, e.g. docetaxel, pemetrexed or erlotinib. In two meta-analyses a significant advantage in progression-free survival and a modest advantage in overall survival were confirmed. However, a balance must be made between possible toxicities and survival advantages for each individual patient.     

Efficacy and safety of first-line erlotinib in elderly patients with advanced non-small cell lung cancer

TaRceva LUng cancer Survival Treatment (TRUST) was an open-label, phase IV study of advanced non-small cell lung cancer (NSCLC). Patients failing or unsuitable for chemotherapy or radiotherapy received erlotinib 150 mg/day until progression. We examined a subpopulation of elderly patients (≥70 years) receiving first-line erlotinib (n=485) in TRUST. In this subpopulation, disease control rate (n=356 with best response data available) was 79% (vs. 69% for the overall TRUST population; p<0.0001); median progression-free survival (PFS) was 4.57 months [95% confidence interval (CI), 3.68-5.22]; median overall survival (OS) was 7.29 months (95% CI, 6.27-8.67); and one-year survival, was 36.6%. PFS and OS were significantly longer in patients developing rash, compared to those without, and in those with good performance status (PS; 0/1), compared to poor PS (≥2). Eighty-seven subpopulation patients (18%) had an erlotinib-related AE; other than the protocol-defined frequent adverse events (AEs); 4% had a grade ≥3 erlotinib-related AE, 7% had an erlotinib-related serious AE. In the subpopulation, dose reductions were required in 27%, most (97%) were reductions to 100 mg/day; treatment was discontinued in 10%, and one death was associated with treatment-related toxicity (<1%). Erlotinib was effective and well-tolerated and may be considered for elderly patients with advanced NSCLC who are unsuitable for standard first-line chemotherapy or radiotherapy.     

Cost description of chemotherapy regimens for the treatment of metastatic pancreas cancer

Multiple chemotherapy regimens are available for the treatment of metastatic pancreas cancer (mPCA). Choice of regimen is based on the patient’s performance status and toxicity profile of the regimen. The objective of this study was to analyze the costs of first-line regimens to further aid in decision-making and develop a platform upon which to assess value. We calculated the monthly cost for individual standard regimens (gemcitabine, gemcitabine/nab-paclitaxel, gemcitabine/erlotinib and FOLFIRINOX) and the overall treatment cost for a course of therapy based on the median progression-free survival achieved in published studies. In addition to cost of drugs, we included administration costs and costs of toxicities (including growth factor support, blood product transfusion and hospitalization for toxicities). Costs for administration and management of adverse events were based on Medicare reimbursement rates for hospital and physician services. Drug costs were based on Medicare average sale prices (all 2014 US$). The monthly costs for gemcitabine, FOLFIRINOX, gemcitabine/erlotinib and gemcitabine/nab-paclitaxel were $1363, $7234, $8007 and $12,221, respectively. The overall treatment costs for a course of the same regimens based on median PFS were $5043, $46,298, $51,004 and $67,216, respectively. The choice of chemotherapy regimen for mPCA should be based on tolerability and efficacy of the regimen individualized to patient’s performance status. Healthcare systems have finite resources; thus, there is increasing emphasis on metrics to define value in health care when outcomes of therapy are similar or produce marked differences in value. These data provide useful financial information to incorporate into the decision-making process.     

Erlotinib in non-small cell lung cancer treatment: current status and future development

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Standard treatment approaches such as chemotherapy, radiotherapy, and surgery have reached a plateau in this disease. Therefore, alternatives to conventional treatment, such as new molecular-targeted therapies, are needed. Targeting the epidermal growth factor receptor (EGFR) has played a central role in advancing NSCLC research, treatment, and patient outcome over the last several years. There are two EGFR tyrosine kinase inhibitors approved for the treatment of advanced NSCLC: gefitinib and erlotinib. Of these, erlotinib has shown a significant improvement in median survival, quality of life, and related symptoms in an unselected population of advanced and metastatic NSCLC patients in the second- or third-line setting. Furthermore, erlotinib has significant antitumor activity in first-line treatment. Moreover, factors that predict the efficacy of erlotinib, including clinical, pathologic, and molecular features, have been investigated. A series of studies is planned to contribute to our understanding of the role of erlotinib in NSCLC treatment. Major areas of clinical research are the assessment of erlotinib: in adjuvant treatment, combined with chemotherapy and/or radiotherapy in locally advanced disease, in the first-line therapy of advanced disease, and in combination and/or sequence with cytotoxic treatments and/or other molecular target agents.     

Systemic chemotherapy for advanced non-small cell lung cancer: recent advances and future directions

Systemic therapy improves the survival and quality of life of patients with advanced stage non-small cell lung cancer (NSCLC). Several new therapeutic options have emerged for advanced NSCLC, incorporating novel cytotoxic agents (taxanes, gemcitabine, pemetrexed) and molecular-targeted agents (erlotinib, bevacizumab). Efforts to improve the outcome of first-line therapy for advanced and metastatic NSCLC have primarily focused on the addition of targeted agents to platinum-based two-drug regimens. Bevacizumab, an antibody against vascular endothelial growth factor, is the first drug to demonstrate superior outcomes when added to systemic chemotherapy in advanced disease. Evaluation of the role of maintenance therapy following four to six cycles of first-line combination chemotherapy is ongoing. Both cytotoxic agents and targeted agents are suitable for evaluation in the maintenance setting. Promising results have been noted with single-agent paclitaxel as maintenance therapy following four cycles of combination therapy with carboplatin and paclitaxel. Phase III studies are now under way to evaluate the roles of gemcitabine, pemetrexed, and erlotinib as maintenance therapies for patients who experience a response or disease stabilization after four cycles of combination chemotherapy. Whether this approach will be successful in extending the survival of a select group of patients remains to be seen.     

Perspectives on salvage therapy for non-small-cell lung cancer

Platinum-based chemotherapy offers a modest survival advantage over best supportive care in chemotherapy-naive patients with a good performance status and advanced/metastatic non-small-cell lung cancer (NSCLC). Despite the survival benefit associated with first-line chemotherapy, the majority of patients will experience relapse or disease progression. In clinicalpractice, an increasing number of patients maintain a good performance status after first-line treatment and are eligible for further treatments. Docetaxel (Taxotere) at 75 mg/m2 given once every 3 weeks has been the standard of care for second-line chemotherapy since the year 2000. Pemetrexed (Alimta) is a novel multitargeted antifolate agent with single-agent activity in first- and second-line treatment of NSCLC. A large phase 111 study comparing docetaxel to pemetrexed in second-line therapy demonstrated that pemetrexed is equally active and less toxic than docetaxel. Based on these results, pemetrexed is a reasonable second-line chemotherapy option for patients with recurrent, advanced NSCLC. Progress made in the field of molecular biology has led to the identification of drugs active against specific cellular targets. Gefitinib (Iressa) and erlotinib (Tarceva) are both orally active tyrosine kinase inhibitors of the epidermal growth factor receptor. Phase II and III trials have demonstrated that these agents are active particularly in a subgroup of patients with specific biologic characteristics. Both drugs have been approved for the treatment of pretreated NSCLC. Other drugs, such as cetuximab (Erbitux) and bevacizumab (Avastin) have shown promising activity in NSCLC and are currently being tested in clinical trials.