Erlotinib in Previously Treated Non–Small-Cell Lung Cancer

Shepherd, Frances A.; Pereira, José Rodrígues; Ciuleanu, Tudor-Eliade; Tan, Eng Huat; Hirsh, Vera; Thongprasert, Sumitra; Campos, Daniel; Maoleekoonpiroj, Savitree; Smylie, Michael; Martins, Renato; Kooten, Maximiliano Van; Dediu, Mircea; Findlay, B.; Tu, Dongsheng; Johnston, D.; Bezjak, Andrea; Clark, Gary M.; Santabárbara, P.; Seymour, Lesley

doi:10.1056/nejmoa050753

Cited by 4,952 publications

(3,526 citation statements)

References 31 publications

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“…28,39,41,241,242 There are two well-established mechanisms of acquired resistance: additional mutations in the EGFR gene, acquired during the course of treatment, which change the protein coding sequence; and amplification of other oncogene signaling pathways, such as those involving the RAS and MET oncogenes. 84,[221][222][223] Kobayashi et al 182 reported a gefitinib-resistant advanced adenocarcinoma patient who had a relapse after 2 years of complete remission with gefitinib.…”

Section: Acquired Resistance To Egfr Tkimentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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Section: Acquired Resistance To Egfr Tkimentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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“…For example, in Caucasian patients, whose overall response rate is 10%, it seems highly sensible to use mutational status as a marker to select the 10-20% of patients who are most likely to benefit from anti-EGFR therapy. Yet, many studies have consistently reported 10% response rates to gefitinib and erlotinib in patients with wild-type EGFR, and the HR of erlotinib to placebo is 0.74 (Zhu et al, 2008), which is comparable to the overall survival benefit of erlotinib in all BR.21 patients (Shepherd et al, 2005). Therefore, it may be that one unifying predictive model does not apply to all patients with NSCLC, and that it is more practical to define different models for patients of various ethnicities.…”

Section: Practical Considerationsmentioning

confidence: 99%

Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors

2009

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“…In the BR.21 study, erlotinib led to a significantly better response rate, median PFS and OS than placebo in the entire previously treated, unselected NSCLC patient population [10]. In the SATURN study, erlotinib maintenance therapy for non-progressive disease after first-line platinum treatment resulted in significantly longer median PFS for the whole study population, and also for the EGFR mutant subgroup [20].…”

Section: Discussionmentioning

confidence: 99%

“…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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Erlotinib in Previously Treated Non–Small-Cell Lung Cancer

Abstract: Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy.

Cited by 4,952 publications

References 31 publications

Molecular pathology of lung cancer: key to personalized medicine

Molecular pathology of lung cancer: key to personalized medicine

Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors

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

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