Erlotinib in Advanced Non-small Cell Lung Cancer: Efficacy and Safety Findings of the Global Phase IV Tarceva Lung Cancer Survival Treatment Study

Reck, Martin; Zandwijk, Nico van; Gridelli, Cesare; Balikó, Zoltán; Rischin, Danny; Allan, Simon; Krzakowski, Maciej; Heigener, David F.

doi:10.1097/jto.0b013e3181f1c7b0

Cited by 118 publications

(104 citation statements)

References 20 publications

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“…The cut-off date for the final analysis was 17 April, 2009. The findings of the study confirmed the favourable efficacy and safety profile of erlotinib in a large heterogeneous population of NSCLC patients; the 1-year survival rate was 37.7%, and median OS and progressionfree survival (PFS) were 7.9 and 3.25 months, respectively (14). The large size of the study database made it feasible to evaluate outcomes among the large number of older patients (≥70 years) who participated; this report describes outcomes among elderly patients who received erlotinib as their first line therapy.…”

Section: Introductionsupporting

confidence: 60%

“…TRUST first-line TRUST AEs, n (%) elderly population overall population (14) Patients with at least one treatment-related AE Other than the pre-specified events defined in the protocol. AE, adverse event; SAE, serious adverse event; TRUST, TaRceva LUng cancer Survival Treatment.…”

Section: Resultsmentioning

confidence: 99%

“…The TaRceva LUng cancer Survival Treatment (TRUST) study was a large, open-label, phase IV study of erlotinib, designed to allow access to erlotinib monotherapy for patients with advanced stage IIIB/IV NSCLC who had previously failed, or were considered unsuitable to receive, standard chemotherapy or radiotherapy, and were ineligible for other erlotinib trials (14). A total of 6,665 patients were enrolled in the study, from 513 centres across 51 countries, and recruitment ceased on 31 May, 2007.…”

Section: Introductionmentioning

confidence: 99%

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

Merimsky¹,

Cheng²,

et al. 2012

Oncology Reports

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Abstract. 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 progressionfree 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 erlotinibrelated 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. IntroductionThe incidence of non-small cell lung cancer (NSCLC) increases with age, with 60% of cases arising in patients over 60 years of age, and 30-40% in patients of 70 years or older (1,2). In developed countries the median age of diagnosis for advanced disease is 68 years (3), but this has increased notably over the last 3 decades. Consequently, the age of the patient is often a major factor for physicians considering treatment options for patients with advanced NSCLC. Elderly patients are often denied therapy, prematurely discontinued and excluded from clinical trials because of the perception that they are less able to tolerate cytotoxic chemotherapy than younger patients, and are more likely to suffer toxic effects that adversely affect their quality of life (4). Physicians may be concerned that age-related impairment in renal or hepatic function could exacerbate the toxic effects of chemotherapy, and that the presence of comorbidities could reduce the capacity of their elderly patients to tolerate such effects. While it is true that the incidence of age-related organ dysfunction and the development of comorbid conditions increase abruptly between 70 and 75 years of age (5), the clinical significance of the relationship between age and comorbid conditions is complex in patients with cancer (6) and it has been suggested that chronological age is not a valid criterion on which to base treatment decisions in NSCLC (7). Clinical trials that have investigated the effects of cytotoxic chemotherapy in unselected elderly patients have reported modest improvements i...

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Section: Introductionsupporting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Merimsky¹,

Cheng²,

et al. 2012

Oncology Reports

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“…Only a few agents including docetaxel, pemetrexed, gefitinib and erlotinib have shown to be effective in the second-line and third-line chemotherapy for advanced NSCLC (Shepherd et al, 2005;Thatcher et al, 2005;Barlesi et al, 2006;Cullen et al, 2008;Kim et al, 2008;Scagliotti et al, 2009;Cappuzzo et al, 2010;Douillard et al, 2010;Reck et al, 2010;Vamvakas et al, 2010). Despite an increasing proportion of patients with advanced NSCLC derive prolonged survival with novel chemotherapy regimens; many of them will require salvage chemotherapy after relapse (Kosmas et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine Plus Paclitaxel as Second-line Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

Baykara¹,

Coşkun²,

Berk³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Purpose: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine 1500 mg/m 2 and paclitaxel 150 mg/m 2 administered every two weeks. Results: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.

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“…Anilinoquinazolines are the most developed class of drugs that inhibit EGFR tyrosine kinase intracellularly 10,11 . Anilinoquinazoline-containing compounds, erlotinib (Tarceva Õ ) 12,13 and gefitinib (Iressa Õ ) 14 have been approved for chemotherapeutic treatment of patients with advanced non-small cell lung cancer. Our strategy is directed toward designing ligands which are structurally similar to the basic skeleton, 4-anilinoquinazoline of erlotinib through replacing quinazoline ring with benzothiazole since both are isosteric with adenine portion of ATP and can mimic the ATP competitive binding regions of EGFR tyrosine kinase.…”

Section: Introductionmentioning

confidence: 99%

Structure-based drug design and biological evaluation of 2-acetamidobenzothiazole derivative as EGFR kinase inhibitor

Gabr

El‐Gohary

El‐Bendary

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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EGFR tyrosine kinase has been reported mainly in 40-80% of non-small lung cancers, in addition to colon and breast cancers. In this study, we illustrate the synthesis of a highly potent antitumor agent. The synthesized compound 4 was screened at NCI, USA, for antitumor activity against non-small lung cancer, colon cancer and breast cancer cell lines. Results indicated that this compound is more potent antitumor agent compared to erlotinib against all tested cell lines except breast cancer (MDA-MB-468) cell line. In addition, it was tested initially at a single dose concentration of 100 mM over 11 different kinases. At this concentration, 94.45% inhibition of the enzymatic activity of EGFR kinase was observed, while the inhibition in activity was below 55% in all other kinases. Compound 4 was further tested in a 10-dose IC 50 mode and showed IC 50 value of 0.239 mM for EGFR kinase. In vivo acute toxicity of this compound was also tested. KeywordsAcetamidobenzothiazole, breast cancer, colon cancer, non-small lung cancer, EGFR tyrosine kinase inhibitor, in vivo acute toxicity History

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Erlotinib in Advanced Non-small Cell Lung Cancer: Efficacy and Safety Findings of the Global Phase IV Tarceva Lung Cancer Survival Treatment Study

Abstract: These data confirm the favorable efficacy and safety profile of erlotinib in a large heterogeneous non-small cell lung cancer population.

Cited by 118 publications

References 20 publications

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

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

Gemcitabine Plus Paclitaxel as Second-line Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

Structure-based drug design and biological evaluation of 2-acetamidobenzothiazole derivative as EGFR kinase inhibitor

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