Symptom Improvement in Lung Cancer Patients Treated With Erlotinib: Quality of Life Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21

Bezjak, Andrea; Tu, Dongsheng; Seymour, Lesley; Clark, Gary M.; Trajković, Aleksandra; Zukin, Mauro; Ayoub, Joseph; Lago, S.; Ribeiro, Ronaldo de Albuquerque; Gerogianni, Alexandra; Cyjon, Arnold; Noble, Jason; Laberge, Francis; Chan, Raymond; Fenton, David; Pawel, Joachim von; Reck, Martin; Shepherd, Frances A.

doi:10.1200/jco.2006.05.8073

Cited by 268 publications

(168 citation statements)

References 28 publications

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“…Several anti-EGFR drugs, such as monoclonal antibodies directed against the extracellular domain and small molecule inhibitors of the receptor-associated tyrosine kinase, have been approved for clinical use (Cunningham et al, 2004;Bezjak et al, 2006). However, a relevant percentage of patients treated with these drugs has no clinical benefit or incurs in the development of acquired resistance.…”

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confidence: 99%

Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs

et al. 2008

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Inhibition of a single transduction pathway is often inefficient due to activation of alternative signalling. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation, survival and angiogenic pathways and has been implicated in the resistance to EGFR inhibitors. Thus, mTOR blockade is pursued to interfere at multiple levels with tumour growth. We used everolimus (RAD001) to inhibit mTOR, alone or in combination with anti-EGFR drugs gefitinib or cetuximab, on human cancer cell lines sensitive and resistant to EGFR inhibitors, both in vitro and in vivo . We demonstrated that everolimus is active against EGFR-resistant cancer cell lines and partially restores the ability of EGFR inhibitors to inhibit growth and survival. Everolimus reduces the expression of EGFR-related signalling effectors and VEGF production, inhibiting proliferation and capillary tube formation of endothelial cells, both alone and in combination with gefitinib. Finally, combination of everolimus and gefitinib inhibits growth of GEO and GEO-GR (gefitinib resistant) colon cancer xenografts, activation of signalling proteins and VEGF secretion. Targeting mTOR pathway with everolimus overcomes resistance to EGFR inhibitors and produces a cooperative effect with EGFR inhibitors, providing a valid therapeutic strategy to be tested in a clinical setting.

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confidence: 99%

Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs

et al. 2008

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“…28 A subsequent analysis of this trial revealed that patients treated with erlotinib had a longer time to deterioration and improved physical function and quality of life compared to BSC. 29 A number of trials have also compared erlotinib to chemotherapy (either docetaxel or pemetrexed) in either unselected or purely EGFR wild-type (EGFRwt) populations. No major trial in unselected or EGFRwt patients has shown erlotinib to be statistically superior to chemotherapy.…”

Section: Egfr Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Second-Line Chemotherapy and Beyond for Non–Small Cell Lung Cancer

Durm

Hanna

2017

Hematology/Oncology Clinics of North America

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Keywordsnon-small cell lung cancer, chemotherapy, second-line treatment, docetaxel, pemetrexed, erlotinib Key Points• Docetaxel, pemetrexed, and erlotinib are approved for the second-line treatment of NSCLC.• The discovery of targetable mutations, the increasing use of maintenance strategies, and the introduction of immunotherapies has made the choice of second-line agents much more complicated.• Ramucirumab with docetaxel is the only combination regimen that has shown improved overall survival in the second-line setting.• Erlotinib is the only agent approved in the third-line setting for EGFR wild-type patients. First Line TreatmentIn patients without targetable genetic alterations, the standard first-line therapy for advanced (stage IIIB or IV) NSCLC is chemotherapy with a platinum doublet for 4-6 cycles with or without bevacizumab. 1 Historically, a number of drugs including paclitaxel, docetaxel, gemcitabine, and vinorelbine were considered acceptable platinum partners in the first-line metastatic setting with essentially no differences in progression free survival (PFS) or overall survival (OS). More recently, additional agents have been approved in combination with platinum in this setting including pemetrexed and nab-paclitaxel. [1][2][3] One particular advance in the last decade has been the recognition that histology should be considered in the choice of initial chemotherapy. This was discovered after an additional analysis of two studies showed pemetrexed to be more effective in non-squamous histologies and less active in squamous tumors. 3-5 Based on these findings, the choice of first-line agents in metastatic NSCLC is now strongly based on presenting histology, and this initial choice affects available second-line options. Maintenance TherapyHistorically, patients treated with first-line platinum doublet chemotherapy who had objective responses or stable disease were placed on surveillance following completion of 4-6 cycles. However, over the last decade, new data suggests that there is benefit to the addition of maintenance therapy following initial chemotherapy. There are two maintenance strategies including continuation of an agent used in the first-line setting or switching to a previously unused agent (switch maintenance). There is data supporting the use of bevacizumab, pemetrexed, and erlotinib in the maintenance setting either as single agents or in combination. [6][7][8][9][10][11] Prior maintenance therapy is of particular importance when discussing second-line chemotherapy options as the use of maintenance therapy, particularly when switch maintenance is employed, influences the availability of agents in the second-line setting and beyond. Chemotherapy as Second-Line TreatmentHistorically, nearly all patients received platinum doublet chemotherapy followed by single agent chemotherapy in the second-line setting. However, with the discovery of targetable mutations, the development of tyrosine kinase inhibitors (TKI), the increasing use of maintenance strategies, and the introduction of imm...

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“…Erlotinib (OSI 744, Tarceva ® , Genentech (Roche), USA) is a potent, orally administered epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), which is well tolerated and has been proven to prolong survival, delay symptom progression and improve quality of life versus placebo in patients with previously treated, advanced NSCLC in a large phase III trial (BR.21) [10,11]. Moreover, erlotinib is more effective as a firstline treatment than standard chemotherapy in patients with exon 19 deletions or exon 21 (L858R) substitution mutations of EGFR [12,13].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

et al. 2014

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a b s t r a c tObjectives: Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients. Materials and methods:MOTIVATE is an open-label, multicenter, observational trial with Tarceva ® (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR). Results and conclusion: In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD.Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%.Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.

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Symptom Improvement in Lung Cancer Patients Treated With Erlotinib: Quality of Life Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21

Abstract: Erlotinib not only improves survival in previously treated patients with NSCLC, but also improves tumor-related symptoms and important aspects of QOL.

Cited by 268 publications

References 28 publications

Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs

Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs

Second-Line Chemotherapy and Beyond for Non–Small Cell Lung Cancer

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

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