Randomized Phase III Trial of Gefitinib versus Docetaxel in Non–Small Cell Lung Cancer Patients Who Have Previously Received Platinum-Based Chemotherapy

Lee

et al. 2010

Cancer

Self Cite

BACKGROUND: Gefitinib and erlotinib are commonly used for salvage therapy in patients with nonsmall cell lung cancer (NSCLC) who have progressed on prior therapies. Although both agents have similar structure and have demonstrated efficacy in NSCLC, gefitinib and erlotinib have not been directly compared in terms of efficacy and other clinical outcomes in patients with NSCLC who have failed prior chemotherapy. This prompted us to analyze the clinical outcomes between gefitinib-treated and erlotinib-treated patients with metastatic or recurrent NSCLC. METHODS: A total of 467 patients with metastatic or recurrent NSCLC who had progressed on prior therapies and received gefitinib or erlotinib therapy between January 2006 and December 2008 were retrospectively reviewed. By using a matched-pair case-control study design, 171 pairs of gefitinib-treated and erlotinib-treated patients were matched according to sex, Eastern Cooperative Oncology Group (ECOG) performance status, histologic type, and smoking history. RESULTS: The median age of all patients was 58 years (range, 20-85 years), and the median ECOG performance status was 1 (range, 0-3). Of 342 patients, 294 (86%) received an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor as second-line or third-line therapy, whereas the remaining 14% had received >2 prior chemotherapy regimens before starting EGFR TK inhibitor therapy. The confirmed overall response rate was 35.1%, and the disease control rate was 64%. With 13.2 months of follow-up, the median overall survival (OS) for the total 342 patients was 12.4 months (95% confidence interval [95% CI], 10.66-14.14 months), and the median progression-free survival (PFS) was 3.2 months (95% CI, 2.65-3.75 months). The overall response rates and disease control rates in the gefitinib-treated and erlotinib-treated groups were 38% versus 32.2% (P ¼.273) and 63.2% versus 64.9%, respectively (P ¼.677). There was no statistically significant difference noted with regard to OS (median, 12.6 vs 12.1 months; P ¼ 0.99) and PFS (median, 4.6 vs 2.7 months; P ¼.06) between the gefitinib-treated and erlotinib-treated groups. CONCLUSIONS: This retrospective analysis shows that gefitinib and erlotinib appear to have similar antitumor activity in terms of response rate and OS in pretreated patients with metastatic or recurrent NSCLC. Further prospective studies are warranted to elucidate any potential differences in toxicity and in dose intensity between gefitiniband erlotinib-treated patients. Cancer 2010;116:3025-33.

Section: Discussionmentioning

confidence: 91%

Comparison of gefitinib versus erlotinib in patients with nonsmall cell lung cancer who failed previous chemotherapy

Lee

et al. 2010

Cancer

Self Cite

“…4, 8 ,9 Furthermore, as second-line chemotherapy, a phase III study demonstrated superior PFS with gefitinib than docetaxel for unselected patients in Korea . 10 . Thus, gefitinib is useful for the firstand second-line treatment of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Prospective Study of Gefitinib Readministration After Chemotherapy in Patients With Advanced Non–Small-Cell Lung Cancer Who Previously Responded to Gefitinib

Koizumi¹,

Agatsuma²,

Ikegami³

et al. 2012

Clinical Lung Cancer

“…In a meta analysis of clinical trials of adjuvant therapy regimens in NSCLC involving .7,000 individuals, first published online in 2008, significant improvements in disease-free survival were demonstrated with relative risks ranging from 0.88 to 0.89 [77]. A more recent literature search of all randomised controlled trials that studied novel adjuvant therapies for patients with NSCLC showed that in 14 studies involving .15,000 patients [78][79][80][81][82][83][84][85][86][87][88][89][90][91], a statistically significant treatment effect on progression-free survival was seen with hazard ratios ranging from 0.6 to 0.83, with a single exception [90] in which the hazard ratio in favour of therapy was reduced to 0.37.…”

Section: The Current Uncertainty About How To Measure Efficacy In Trimentioning

confidence: 99%

A progression-free end-point for idiopathic pulmonary fibrosis trials: lessons from cancer

Vancheri

Bois

2012

Eur Respir J

Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease that results in increasing morbidity. To date there is only one licensed therapy for this condition and other agents are needed for this attritional disease. Efforts to study other agents have been obstructed by an increasing division of opinion about the most clinically meaningful end-point of phase III clinical trials to demonstrate efficacy. Many clinicians believe that an agent that impedes progression of the disease is more than acceptable and will encourage the pharmaceutical industry to further develop their IPF programmes. We have been impressed by the behavioural and biological similarities of cancer and IPF, and wondered if lessons could be learned about clinical trial design from lung cancer studies. Here, we set out our arguments that the similarities with cancer justify comparing the magnitude of therapeutic effects in clinical trials in nonsmall cell lung cancer with those in successful trials in IPF. We demonstrate that efficacy is of a similar magnitude in the two chronic lung diseases. We recommend that the demonstration of similar magnitudes of progression-free disease effect in IPF, using appropriate indices, should be considered as clinically meaningful benefit in future phase III clinical trials of novel therapies.KEYWORDS: Clinical trials, fibroblast/myofibroblast, forced vital capacity, lung cancer, pulmonary fibrosis, pulmonary function tests I diopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease characterised by an accumulation of myofibroblasts in the alveolar wall, aberrant matrix deposition and subsequent distortion of the normal lung architecture. The disease results in progressive morbidity, worsening quality of life and an increasing dependence on others for the most basic of functional needs. The current paradigm of the pathogenetic process that results in IPF is that the disease is initiated by recurrent injury to the alveolar epithelium and evolves into an aberrant fibroproliferative response which progresses [1]. The cause(s) of the repeated injury is unknown but is thought to be the product of one or more environmental triggers operating within an individual whose genotype makes them susceptible to the disease [2]. More recently, IPF has been assimilated to a neoproliferative disorder based on the evidence that a number of pathogenic features of IPF are shared with cancer biology [3]. Genetic and epigenetic changes, delayed apoptosis and altered response to regulatory signals by myofibroblasts, reduced cellular communications and abnormal activation of specific signalling pathways have been shown to be hallmarks common to IPF and cancer. Consistent with this, COOL et al. [4] reported that ''fibroblast foci'', the characteristic defining lesions in IPF, are interconnected, forming a three-dimensional reticulum that resembles the tissue infiltration typical of cancer. The absence of monoclonality noted within the fibroblast foci and their incapacity to metastasise ...