Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study

Ciuleanu, Tudor-Eliade; Stelmakh, L.; Cicėnas, Saulius; Miliauskas, Skaidrius; Grigorescu, Alexandru; Hillenbach, Carina; Johannsdottir, Hrefna Kristin; Klughammer, Barbara; Esteban, Emilio

doi:10.1016/s1470-2045(11)70385-0

Cited by 328 publications

(280 citation statements)

References 16 publications

Supporting

Mentioning

263

Contrasting

Unclassified

Order By: Relevance

“…Recently, ınvestigators undertook the Tarceva in treatment of advanced NSCLC study to assess the efficacy and tolerability of second-line erlotinib versus chemotherapy in patients with refractory NSCLC (Ciuleanu et al, 2012). No significant differences in efficacy were noted between patients treated with erlotinib and patients treated with docetaxel or pemetrexed.…”

Section: Discussionmentioning

confidence: 99%

“…Still, the role of erlotinib is controversial in patients with unknown EGFR mutational status (Karam et al, 2012). Other than the BR.21 trial, other studies have established erlotinib as a standard, even in patients without mutational analysis (Shepherd et al, 2005;Cappuzzo et al, 2010;Ciuleanu et al, 2012). On the other hand, little attention has been given to the prognostic factors for patients with NSCLC in this era of molecular-targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

Aydıner

Yıldız²,

Seyidova³

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: The efficacy of erlotinib is controversial in patients with unknown EGFR mutational status. The aim of this study was to identify the clinicopathological factors that are predictive of erlotinob treatment outcomes for NSCLC patients with unknown EGFR mutational status. Materials and Methods: A retrospective analysis of 109 patients with advanced NSCLC who had previously failed at least one line of chemotherapy and received subsequent treatment with erlotinib (150 mg/day orally) was performed. A Cox proportional hazard model for univariate and multivariate analyses was used to identify the baseline clinical parameters correlating with treatment outcome, expressed in terms of hazard ratios (HRs) and 95% confidence intervals. Results: The median treatment duration was 15 weeks (range, 4-184). The disease control rate was 55%, including disease stability for ≥3 months for 40% of the patients. Median progression-free survival and median overall survival (OS) were 4.2 and 8.5 months, respectively. The Cox model indicated that an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.82; p<0.001), presence of intra-abdominal metastasis (HR 3.42; p=0.002), 2 or more prior chemotherapy regimens (HR 2.29; p=0.021), and weight loss >5% (HR 2.05; p=0.034) were independent adverse prognostic factors for OS in NSCLC patients treated with erlotinib. Conclusions: This study suggests that NSCLC patients should be enrolled in erlotinib treatment after a first round of unsuccessful chemotherapy to improve treatment success, during which they should be monitored for intra-abdominal metastasis and weight loss.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

Aydıner

Yıldız²,

Seyidova³

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…However, during the past few decades, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been proved to be an effective choice for patients with EGFR mutation. The clinical benefit of the targeting EGFR signaling pathways for advanced NSCLC patients has been validated proved (5,6). The first-generation TKIs have become the standard first-line treatment for NSCLC patients with EGFR mutation, including the reversible inhibitors, gefitinib and erlotinib.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and toxicity of afatinib in advanced EGFR-positive non-small-cell lung cancer patients after failure of first-generation tyrosine kinase inhibitors: a systematic review and meta-analysis

et al. 2017

View full text Add to dashboard Cite

Background: The first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs), gefitinib and erlotinib, have become the standard first-line treatment for non-small-cell lung cancer (NSCLC) patients with EGFR mutation. However, there was no pooled analysis focused on the usage of the second-generation TKI, afatinib, in advanced EGFR-positive NSCLC patients after failure of first generation TKIs. Therefore, a meta-analysis was conducted to solve the above question. Methods: Electronic databases were searched for eligible literatures. ORR (objective response rate), DCR (disease controlled rate), PFS (progression-free survival), OS (overall survival) and primary grade 3/4 adverse events were pooled with the corresponding 95% confidence interval using R software. Sensitivity analyses and heterogeneity were quantitatively evaluated. Results: A total of 545 EGFR-positive patients were available for analysis from five studies after detailed screening from 909 relevant studies. The pooled ORR and DCR of afatinib in EGFR-positive patients after failure of the first generation EGFR-TKIs were 0.12 (0.08-0.19) and 0.60 (0.53-0.68), respectively. Besides, the 6 m-PFS rate, 1 y-PFS rate and 6 m-OS rate were 0.26 (0.22-0.30), 0.08 (0.06-0.10) and 0.74 (0.56-0.86). The grade 3/4 rate of diarrhea and that of skin deformity were 0.23 (0.10-0.46) and 0.14 (0.05-0.33), respectively. Sensitivity analyses revealed similar results with lower heterogeneity. Conclusions: Considering the efficacy, toxicity and current availability, afatinib could be a therapeutic option for advanced EGFR mutated NSCLC patients after the failure of 1st-generation TKIs.

show abstract

“…No difference was found between the two groups with respect to median OS, neither for the whole population, nor for EGFR WT patients. Nevertheless, the risk of death was lower in the erlotinib group of the KRAS WT population (p = 0.041) [26]. The objective tumor response rate of the erlotinib-arm in the TAILOR study was 3% [23].…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study

Cited by 328 publications

References 16 publications

Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

The efficacy and toxicity of afatinib in advanced EGFR-positive non-small-cell lung cancer patients after failure of first-generation tyrosine kinase inhibitors: a systematic review and meta-analysis

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

Contact Info

Product

Resources

About