Treatment Of Non-squamous Non-small Cell Lung Cancer Research Articles

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057

BackgroundNivolumab, a programmed death-1 inhibitor, prolonged overall survival and had a favourable safety profile versus docetaxel in previously treated patients with advanced non-squamous non-small cell lung cancer (NSCLC) in the phase III CheckMate 057 trial. AimTo evaluate health-related quality of life (HRQoL) using patient-reported outcomes. MethodsDisease-related symptoms and general health status were assessed using two validated patient-reported instruments, the Lung Cancer Symptom Scale (LCSS) and the European Quality of Life Five Dimensions (EQ-5D), respectively. The proportion of patients with disease-related symptom improvement at 12 weeks on the LCSS average symptom burden index (ASBI) was a secondary end-point. LCSS 3-item global index (3-IGI), EQ-5D utility index and EQ-5D visual analogue scale (VAS) scores were also determined. Mixed-effects model repeated measures (MMRM) and time to first deterioration analyses assessed longitudinal changes. ResultsMean baseline LCSS ASBI scores were similar in both arms. By week 12, rates of disease-related improvement (95% confidence interval) were similar between nivolumab (17.8% [13.6–22.7]) and docetaxel (19.7% [15.2–24.7]); however, numerical differences in LCSS ASBI mean change from baseline favoured nivolumab. Subsequently, LCSS ASBI scores improved with nivolumab and worsened with docetaxel, with statistically significant between-arm differences at weeks 12, 24, 30 and 42. HRQoL improvements with nivolumab versus docetaxel were also supported by the LCSS 3-IGI, EQ-5D VAS and MMRM analysis. Time to first HRQoL deterioration was longer with nivolumab than with docetaxel. ConclusionNivolumab improved disease-related symptoms and overall health status versus docetaxel for second-line treatment of advanced non-squamous NSCLC. Clinical trial registrationNCT01673867.

Efficacy and Safety of Bevacizumab Combined with Chemotherapy as Second-line or Later-line Treatment in Advanced Nonsquamous Non-small Cell Lung Cancer

背景与目的贝伐珠单抗联合含铂双药化疗被推荐为无驱动基因的晚期非鳞非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的一线治疗方案，但此方案用于二线及以上非鳞NSCLC的研究并不普遍。本研究拟探讨二线及以上应用贝伐珠单抗联合化疗治疗晚期非鳞NSCLC的疗效和安全性。方法回顾性分析郑州大学附属肿瘤医院2014年1月-2017年6月间一线治疗进展后应用贝伐珠单抗的晚期非鳞NSCLC患者的临床资料，采用Kaplan-Meier法、Log-rank检验和Cox模型进行统计分析。结果这项研究共纳入62例患者，总体的客观缓解率（objective response rate, ORR）为32.2%，疾病控制率（disease control rate, DCR）为96.8%。中位无进展生存期（progression-free survival, PFS）为6.4个月（95%CI: 6.05-6.83），中位总生存期（overall survival, OS）为20.4个月（95%CI: 12.98-27.76）。在亚组分析中，脑转移患者与无脑转移患者的中位PFS差异无统计学意义（6.2个月vs 6.4个月，P=0.052）。贝伐珠单抗的应用周期（> 6个或≤6个）是PFS的独立影响因素（P=0.004）。最常见的不良反应有白细胞减少、乏力、恶心、血小板减少和高血压。结论二线及以上应用贝伐珠单抗联合化疗治疗晚期非鳞NSCLC的疗效显著且安全性良好。

Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC

BackgroundThe cancer-cell–killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor–mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non–small-cell lung cancer (NSCLC) who had not previously received chemotherapy.MethodsWe randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group.ResultsIn the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P<0.001); the corresponding values in the Teff-high WT population were 11.3 months and 6.8 months (hazard ratio, 0.51 [95% CI, 0.38 to 0.68]; P<0.001). Progression-free survival was also longer in the ABCP group than in the BCP group in the entire intention-to-treat population (including those with EGFR or ALK genetic alterations) and among patients with low or negative programmed death ligand 1 (PD-L1) expression, those with low Teff gene-signature expression, and those with liver metastases. Median overall survival among the patients in the WT population was longer in the ABCP group than in the BCP group (19.2 months vs. 14.7 months; hazard ratio for death, 0.78; 95% CI, 0.64 to 0.96; P=0.02). The safety profile of ABCP was consistent with previously reported safety risks of the individual medicines.ConclusionsThe addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status. (Funded by F. Hoffmann–La Roche/Genentech; IMpower150 ClinicalTrials.gov number, NCT02366143.)

Treatment patterns and cost-effectiveness of first line treatment of advanced non-squamous non-small cell lung cancer in Medicare patients

Aim: To assess the cost-effectiveness of first-line pemetrexed/platinum and other commonly administered regimens in a representative US elderly population with advanced non-squamous non-small cell lung cancer (NSCLC).Materials and methods: This study utilized the Surveillance Epidemiology and End Results (SEER) cancer registry linked to Medicare claims records. The study population included all SEER-Medicare patients diagnosed in 2008–2009 with advanced non-squamous NSCLC (stages IIIB–IV) as their only primary cancer and who started chemotherapy within 90 days of diagnosis. The study evaluated the four most commonly observed first-line regimens: paclitaxel/carboplatin, platinum monotherapy, pemetrexed/platinum, and paclitaxel/carboplatin/bevacizumab. Overall survival and total healthcare cost comparisons as well as incremental cost-effectiveness ratios (ICERs) were calculated for pemetrexed/platinum vs each of the other three. Unstratified analyses and analyses stratified by initial disease stage were conducted.Results: The final study population consisted of 2,461 patients. Greater administrative censorship of pemetrexed recipients at the end of the study period disproportionately reduced the observed mean survival for pemetrexed/platinum recipients. The disease stage-stratified ICER analysis found that the pemetrexed/platinum incurred total Medicare costs of $536,424 and $283,560 per observed additional year of life relative to platinum monotherapy and paclitaxel/carboplatin, respectively. The pemetrexed/platinum vs triplet comparator analysis indicated that pemetrexed/platinum was associated with considerably lower total Medicare costs, with no appreciable survival difference.Limitations: Limitations included differential censorship of the study regimen recipients and differential administration of radiotherapy.Conclusions: Pemetrexed/platinum yielded either improved survival at increased cost or similar survival at reduced cost relative to comparator regimens in the treatment of advanced non-squamous NSCLC. Limitations in the study methodology suggest that the observed pemetrexed survival benefit was likely conservative.

Oral vinorelbine plus cisplatin versus pemetrexed plus cisplatin as first-line treatment of advanced non-squamous non-small-cell lung cancer: cost minimization analysis in 12 European countries

Objective: A combination of vinorelbine and cisplatin is a standard treatment in non-small-cell lung cancer; oral vinorelbine is registered in 45 countries. Pemetrexed and cisplatin are recommended in front-line chemotherapy of non-squamous non-small-cell lung cancer (NS-NSCLC). The objective of this study was to conduct a cost minimization analysis from the perspective of the national health service (NHS) in each of 12 European countries, based on a randomized phase II study in NS-NSCLC (NAVoTRIAL01), with 100 oral vinorelbine plus cisplatin patients (arm A) and 51 pemetrexed plus cisplatin patients (arm B).Research design and methods: Country-specific costs and DRG codes considered included those relating to anticancer drugs, administration settings (out-patient/in-patient/at home), serious adverse events (defined as involving hospitalization and considered due to anticancer drugs) and concomitant medications. Relevant costs were calculated based on country-specific reimbursement procedures and official tariffs.Main outcome measures: Cost and savings per patient.Results: Using the NHS perspective, savings per patient treated with oral vinorelbine ranged from €1317 (Denmark) to €35,001 (Germany). Expressed as percentages, savings per patient treated with oral vinorelbine compared with pemetrexed ranged between 5% (France) and 83% (Czech Republic). Pooled average costs for each treatment arm across the 12 countries resulted in cost savings for payers of €12,871, favoring oral vinorelbine plus cisplatin.Conclusions: Given the reported efficacy with both regimens, this pan-European economic analysis provides compelling evidence supporting oral vinorelbine use over pemetrexed for the treatment of NS-NSCLC. Oral vinorelbine provides similar efficacy and an easily manageable safety profile at lower overall cost per patient treated, combined with an easier/more convenient mode of administration. Sensitivity analysis across varied scenarios demonstrated the robustness of the results. The principle weakness of our study was its reliance upon a single small scale study to provide efficacy data, since this is the only study conducted in this specific population of patients. Further large scale trials are needed to confirm these results.

Feasibility study of first-line chemotherapy using Pemetrexed and Bevacizumab for advanced or recurrent nonsquamous non-small cell lung cancer in elderly patients: TORG1015.

BackgroundThe addition of bevacizumab to cytotoxic agents prolongs survival in patients with nonsquamous non-small cell lung cancer (NSCLC). To date, there is no evidence to suggest that treatment with a cytotoxic agent plus bevacizumab is more effective than a cytotoxic agent alone for nonsquamous NSCLC in elderly patients. We conducted a feasibility study of pemetrexed plus bevacizumab as a first-line treatment for advanced or recurrent nonsquamous NSCLC in elderly patients.MethodsMajor eligibility and exclusion criteria included: chemotherapy-naive status; non-fitness for bolus combination chemotherapy; stage III/IV or relapsed nonsquamous NSCLC; age ≥70; performance status 0–1; absence of brain metastasis; and no history of hemoptysis and thoracic irradiation. Pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered intravenously on day 1, and repeated every 3 weeks thereafter. The primary endpoint was safety, and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the percentage of patients who completed ≥3 cycles.ResultsFrom October 2010 to April 2012, a total of 12 patients were enrolled. No dose-limiting toxicity or treatment-related deaths were observed. Three patients achieved PR, and the ORR was 25 %. The median PFS and OS were 5.4 months (95 % CI 1.1–8.8 months) and 13.6 months (95 % CI 5.3–15.6 months), respectively. Seven of 12 patients (58 %) received ≥3 cycles.ConclusionsPemetrexed plus bevacizumab in the treatment of elderly patients with nonsquamous NSCLC was well tolerated and shows promise as first-line treatment.Trial registrationUMIN Clinical Trial Registry; UMIN000004263. Registered on 25 September, 2010.

Treatment of Advanced and Metastatic Squamous Non-small Cell Lung Cancer

Lung cancer is a disease with a poor prognosis, and is the leading cause of cancer-related death in Korea as well as the USA. Unlike non-squamous non-small cell lung cancer (NSCLC), squamous NSCLC rarely harbors epidermal growth factor receptor and anaplastic lymphoma kinase mutations for which directed molecular targeted therapies are available. Traditional cytotoxic chemotherapy drugs, including cisplatin, have been approved for use in the treatment of advanced and metastatic squamous NSCLC. The second-generation regimens—gemcitabine, paclitaxel, docetaxel, and vinorelbine with cisplatin—are standard first-line treatments for advanced and metastatic squamous NSCLC. Docetaxel was approved for second-line treatment in 1999. Addition of the anti-angiogenic agent, ramucirumab, to docetaxel showed improved survival in squamous cell NSCLC patients in the second-line setting compared with single-agent docetaxel. The immune checkpoint inhibitor-programmed cell death-1 inhibitor, nivolumab, is currently approved for squamous cell NSCLC. Pembrolizumab also received FDA approval for treatment of NSCLC cases in which tumor tissue is positive for programmed cell death-ligand 1 expression. Keywords: Neoplasm, Squamous cell; Lung neoplasms; Drug therapy; Angiogenesis inhibitors; Immunotherapy 중심 단어: 편평상피세포암; 폐암; 약물 치료; í˜ˆê´€í˜•ì„±ì–µì œì œ; 면역 치료

First-Line Pemetrexed Plus Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in East Asian Never-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-cell Lung Cancer: Quality of Life Results From a Randomized Phase III Trial

BackgroundThe efficacy results from an open-label, randomized, multicenter study found no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) and unknown epidermal growth factor receptor (EGFR) mutation status (hazard ratio favored PC/G). The present report describes the quality of life (QoL) results from that trial. Patients and MethodsChemotherapy-naive, East Asian, light ex-smokers or never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status (n = 236) were randomly assigned (1:1) to PC/G or G. EGFR mutation status was subsequently determined for 74 patients. The symptoms and QoL were assessed using the Lung Cancer Symptom Scale (LCSS). The time to worsening of symptoms (TWS) was analyzed using the Kaplan-Meier method. ResultsIn the overall population, the TWS was generally longer in the G group (n = 109) than in the PC/G group (n = 109) for the LCSS symptoms classified as treatment-related (loss of appetite, fatigue) and tumor-related (cough, dyspnea, hemoptysis, pain). In the subgroup of patients with wild-type EGFR, the TWS was generally longer in the PC/G group (n = 13) than in the G group (n = 8) for the tumor-related LCSS symptoms. ConclusionIn this study population clinically selected to respond to gefitinib, the LCSS scores were more favorable in the G group than in the PC/G group. Patients with wild-type EGFR tended to show greater improvement in tumor-related LCSS symptoms with chemotherapy than with gefitinib alone. These LCSS outcomes provide further evidence that patients with wild-type EGFR might not benefit from first-line treatment of advanced NSCLC with gefitinib.

Assessment of chemotherapy strategy using bevacizumab for non-squamous non-small cell lung cancer in a real-world setting: A multi-institutional observational study

Abstract Micro-abstract We retrospectively analyzed 162 patients with non-squamous non-small cell lung cancer (NSCLC) who underwent first-line chemotherapy with bevacizumab (BEV); 127 patients without driver oncogenes, 17 patients with EGFR major mutations, 12 patients with ALK rearrangements, 4 patients with EGFR minor mutations and 2 patients with rare types of histology. Background BEV has been approved for treatment of non-squamous NSCLC and is authenticated as one of the key drugs in the treatment of advanced non-squamous NSCLC. Patients and methods We retrospectively analyzed patients with stage IIIB/IV non-squamous NSCLC who underwent chemotherapy with BEV in first-line setting. Results In 162 patients who underwent chemotherapy combined with BEV as first-line treatment, the median overall survival (OS) and progression-free survival (PFS) were 23.5 months and 6.8 months, respectively. The PFS did not differ significantly by the presence of driver oncogenes. In patients without driver oncogenes, more patients who received carboplatin plus pemetrexed with BEV could complete at least 4 cycles of induction therapy and more of these patients proceeded to maintenance therapy than those who received carboplatin plus paclitaxel with BEV, which resulted in better outcome associated with carboplatin plus pemetrexed with BEV. Continuation of BEV beyond first progression did not show any survival benefit. In EGFR mutation-positive patients, the order of BEV-containing regimen and TKI did not influence on OS. None of 18 patients with brain metastases detected at diagnosis developed intracranial hemorrhage. Conclusions PFS of first-line chemotherapy using BEV was not influenced by the existence of driver oncogenes. In patients without driver mutations in real clinical practice, as the first-line partner regimen with BEV, carboplatin plus pemetrexed may be more feasible as compared to carboplatin plus paclitaxel. BEV use beyond first progression did not deliver significant survival benefit. BEV was safe for brain metastases.

Molecular landscape of non-squamous, non-small cell carcinoma of the lung

The treatment of advanced or metastatic non-small cell lung cancer (NSCLC) has undergone a major change over the past decade, from a single option of platinum-based systemic chemotherapy to an increasingly personalized approach to treatment based on specific molecular alterations within tumors. The scope of this paper is to review the literature on the treatment of non-squamous NSCLC and give a broad understanding of the current molecular targets for which therapies currently exist, as well as other targets for which therapies may soon be developed. Additionally, issues of resistance with targeted therapies will be discussed. This manuscript only summarizes the work done to date, and in no way is meant to be comprehensive.

Pemetrexed-based chemotherapy in advanced nonsquamous non-small cell lung cancer (NSCLC).

e22245 Background: Pemetrexed in combination with platinum chemotherapy is an indicated regimen for treatment of adv non-squamous NSCLC. The purpose of this study is to evaluate the efficacy of pem...

Squamous non-small cell lung cancer as a distinct clinical entity.

Traditionally, the treatment of lung cancer has been based on histologic type [non-small cell lung cancer (NSCLC) or small cell lung cancer], performance status, and stage of disease. However, more recently, treatment decisions are being made based on molecular and histologic characteristics of the tumor. Specifically, the subclassification of NSCLC as squamous or nonsquamous is important in the context of newer treatments because clinical data have demonstrated differences in the tolerability and activity of these agents. Although progress continues to be made in the treatment of nonsquamous NSCLC, a significant unmet need exists for patients with squamous NSCLC. For both targeted and chemotherapeutic agents, the majority of regulatory approvals and updates to clinical practice guidelines for advanced NSCLC have focused on nonsquamous disease. In addition, because of safety concerns, patients with squamous NSCLC have been excluded from a number of clinical trials of investigational agents, particularly those targeting angiogenesis. This review discusses the importance of histology for treatment selection in NSCLC and summarizes recently completed and ongoing trials of investigational agents in squamous NSCLC. In addition, exciting developments in next-generation sequencing of squamous NSCLC have highlighted differences between squamous and nonsquamous disease and revealed potential new therapeutic targets. Advances in the molecular genetics of squamous NSCLC and implications for therapy will also be reviewed. Although progress in squamous NSCLC has faced limitations, momentum is building toward the identification of more effective treatments for this patient population.

Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer.

Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR) mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be a pivotal drug when a combination maintenance therapy is used in practice. For future maintenance therapy, we need to explore reliable predictive selection or exclusion markers that can predict who will really benefit from maintenance therapy.

Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter randomized trial

CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor (EGFR). Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m(2)) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data. From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40-0.75, P < 0.001] as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38-0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49-1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43-2.08, P = 0.877). CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients. NCT00891579.

P8. Efficacy of first-line pemetrexed/platinum chemotherapy in the treatment of advanced NSCLC in routine clinical practice.

Background It is well known that patients with advanced non-squamous non-small cell lung cancer (NSCLC) benefit substantially from platinum-based chemotherapy containing pemetrexed (pem/platinum ChT). Additionally, maintenance therapy with pemetrexed further improves survival in patients with clinical benefit (CB) to induction Cht. Evidence based data show that using pem instead of gemcitabine and maintenance therapy approach improves survival rates in pts with advanced non-squamous NSCLC to around 13 months (mo). The aim of our observational study was to evaluate the efficacy of first line pem/platinum in advanced non-squamous NSCLC treated in routine clinical practice.

Activation of Nrf2 pathways correlates with resistance of NSCLC cell lines to CBP501 in vitro.

CBP501 is an anticancer drug candidate that was investigated in two randomized phase II clinical trials for patients with nonsquamous non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). CBP501 has been shown to have two mechanisms of action, namely calmodulin modulation and G2 checkpoint abrogation. Here, we searched for a biomarker to predict sensitivity to CBP501. Twenty-eight NSCLC cell lines were classified into two subgroups, CBP501-sensitive and -insensitive, by quantitatively analyzing the cis-diamminedichloro-platinum (II) (CDDP)-enhancing activity of CBP501 through treatments with short-term (1 hour) coexposure to CDDP and CBP501 or to either alone. Microarray analysis was performed on these cell lines to identify gene expression patterns that correlated with CBP501 sensitivity. We found that multiple nuclear factor erythroid-2-related factor 2 (Nrf2) target genes showed high expression in CBP501-insensitive cell lines. Western blot and immunocytochemical analysis for Nrf2 in NSCLC cell lines also indicated higher protein level in CBP501-insensitive cell lines. Moreover, CBP501 sensitivity is modulated by silencing or sulforaphane-induced overexpression of Nrf2. These results indicate that Nrf2 transcription factor is a potential candidate as a biomarker for resistance to CBP501. This study might help to identify those subpopulations of patients who would respond well to the CBP501 and CDDP combination treatment of NSCLC.

Outcomes of an Australian testing programme for epidermal growth factor receptor mutations in non‐small cell lung cancer

Molecular characterisation of non-squamous non-small-cell lung cancer (NSCLC) is required to direct optimal treatment. Treatment of NSCLC with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase (EGFR-TKI) should be guided by the presence of activating mutations of the EGFR gene. To gain insight into the rate of testing, the range of tissues samples, test utility and outcome when cost of testing as a barrier to access is removed in the Australian setting. In October 2010, a sponsored programme was commenced to gather data on EGFR gene mutation testing in Australia. Partnering laboratories were funded for provision of de-identified results. For participating patients, the programme supported the test charge. Mutation testing was performed using Sanger sequencing of exons 18-21 of the EGFR. Samples 2013 were submitted from 2012 patients. Full sequencing was achieved in 1717 (85%). Failure of full sequencing was more likely in samples derived from fine needle aspiration(FNA) biopsy than tissue biopsy or pleural/pericardial fluid cell blocks OR 3.1 (95% CI 1.9-5.2). There were 359 mutations seen in 337 patients. 14.5% of cases had a classical mutation conferring sensitivity to EGFR-TKI. In addition there was a range of less common mutations - some predicting responses and others of uncertain significance. 1.4% of cases had mutations associated with non-responsiveness to EGFR-TKI. EGFR gene mutation testing is feasible on local and interstate lung cancer samples. The rate of valid test outcomes is high, but FNA samples are associated with more frequent test failure.

Phase II study of bevacizumab, cisplatin, and pemetrexed as first-line chemotherapy for advanced nonsquamous non-small cell lung cancer (NS-NSCLC) with EGFR wild-type.

e19125 Background: AVAPER trial demonstrated that a bevacizumab, cisplatin and pemetrexed combination regimen (CDDP/PEM/BEV) is beneficial in advanced nonsquamous non-small-cell lung cancer (NS-NSCLC), but there are few reports of the regimen, which combined these agents. The aim of this phase II study was to evaluate the feasibility and safety of a CDDP/PEM/BEV regimen in the treatment of NS-NSCLC with EGFR wild type in Japanese patients. Methods: Patients with stage III and IV NS-NSCLC with EGFR wild type were treated with CDDP/PEM/BEV. Chemotherapy treatments consisted of 4-6 cycles of CDDP 75mg/m2, pemetrexed 500mg/m2 and bevacizumab 15mg/kg on day 1 every 3 - 4 weeks. The primary endpoint of this study was the response rate and the secondary endpoint was PFS, OS and rates of adverse events. Results: Twenty-five patients were enrolled between August 2010 and February 2013. The patient’s demographics were: median age 62 years (range 42-70), 19 males and 6 females. 4 cases were stage III and 21 cases we...

First-line crizotinib versus pemetrexed–cisplatin or pemetrexed–carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014)

8002 Background: The efficacy of the oral ALK inhibitor crizotinib as 1st-line treatment for advanced ALK-positive NSCLC compared with standard chemotherapy is unknown. A multicenter, randomized op...

L’association paclitaxel–bevacizumab est une alternative intéressante dans le traitement des cancers bronchopulmonaires non épidermoïdes avancés en troisième ligne et plus

Bevacizumab is recommended in first line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). Paclitaxel is a doublet drug also widely used in cisplatin-based regimens. Paclitaxel plus bevacizumab is a standard regimen as first line treatment of metastatic breast cancer. Since there is no guideline for third line treatment of NSCLC, some oncology units use paclitaxel-bevacizumab in some NSCLC patient after relapse of the second line. The aim of this study was to assess retrospectively the feasibility and efficacy of this treatment option in stage IV NSCLC. Patients who had received the combination of paclitaxel (80 to 90 mg/m(2) in a weekly schedule) and bevacizumab (7.5 to 15 mg/kg every 21 days) in the thoracic oncology departments of two university hospitals in the Rhone-Alpes Department were retrospectively reviewed. Twelve patients underwent this treatment. Their mean age was 56 years and their performance status was less or equal to 1 in 50 % of the cases. The chemotherapy was given as fifth line in 67 % of the patients and 67 % were antiangiogenic naïve. They received a mean of 6 courses. The overall response rate was 33 % and the disease control rate 66 %. Median progression-free survival was 5.1 months (95 %CI 1.0-9.1). Ten patients (82 %) experienced toxicity, the majority grade 1 to 2 events, and only one a grade 3 event (febrile neutropenia). There were no severe bleeding episodes. Combined paclitaxel-bevacizumab chemotherapy seems feasible in patients with NSCLC. The toxicity profile is acceptable. This regimen should be evaluated in further prospective studies.