Different Efficacies of Erlotinib and Gefitinib in Taiwanese Patients with Advanced Non-small Cell Lung Cancer: A Retrospective Multicenter Study

Fan, Wei; Yu, Chong Jen; Tsai, Chun Ming; Huang, Ming Shyan; Lai, Ching‐Huang; Hsia, Te Chun; Tien, Yin Jing; Huang, Shiang Fen; Wu, Chieh Hung; Chou, Kun-Ta; Lee, Yu Chin; Perng, Reury Perng; Chen, Yuh Min

doi:10.1097/jto.0b013e3181f77b27

Cited by 25 publications

(31 citation statements)

References 33 publications

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“…Our previous findings of a similar response rate, better disease control rate, longer PFS and overall survival, in a multi-center, retrospective analysis of NSCLC patients with unknown tumor EGFR mutation status, were again partially documented in the present study. There was an improved response rate and longer PFS in patients without tumor EGFR-activating mutations (17). This effectiveness in patients without EGFR-activating mutations is supported by cell line findings and is also possibly due to the higher dose intensity of erlotinib than gefitinib.…”

supporting

confidence: 70%

“…An effect on overall survival in genotypically uncharacterized NSCLC patients was observed with erlotinib (BR.21 trial) (3), but not gefitinib (ISEL trial) (2), although the response rates were similar. Several possible explanations have been offered, and the focus has mainly been on the suboptimal dosage of gefitinib (17). Erlotinib was administered at its maximum tolerated dose (MTD), while gefitinib was administered at approximately one third of its MTD (13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

“…The varying overall survival outcomes with these two drugs compared with the placebo were widely debated, although gefitinib demonstrated a significant survival benefit in a subgroup of patients of Asian origin (4). There are many possible reasons for this difference in survival, including the most frequently mentioned -that the dose intensity or drug concentrations are higher in patients receiving erlotinib treatment than in those receiving gefitinib treatment (13)(14)(15)(16)(17). Phase III, randomized trials comparing gefitinib or erlotinib with docetaxel or pemetrexed have been performed, but the superiority of one agent over the other has not been documented (5,18,19 …”

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confidence: 99%

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Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations

Chen

Tsai

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an effective treatment for advanced non-small cell lung cancer. The objective of the present study was to compare the efficacy of gefitinib and erlotinib in patients with pulmonary adenocarcinoma, whose tumor EGFR mutation status was known. Pulmonary adenocarcinoma patients who began receiving gefitinib or erlotinib treatment from January 2005 to December 2010, and whose tumor EGFR mutation status had been determined, were included. Clinical data, type of treatment response and survival time data were collected. Of the 224 patients enrolled, 124 received gefitinib treatment and 100 received erlotinib treatment. Of these patients, 146 individuals had tumors with EGFR-activating mutations (exon 19 deletions and/point mutation of L858R in exon 21) and 78 did not. There was no difference in treatment response whether or not the patients had tumors with EGFR-activating mutations at the time they received gefitinib or erlotinib treatment. The median progression-free survival (PFS) of the gefitinib and erlotinib groups was 7.6 and 7.9 months, respectively (p=0.4731). PFS was significantly longer for patients without EGFR-activating mutations who received erlotinib treatment (n=48; median, 4.5 months) than for those who received gefitinib treatment (n=30; median, 2.3 months), with a hazard ratio of 0.58 (95% CI, 0.35-0.96; p=0.0339). Patients whose tumors had EGFR-activating mutations displayed no difference in PFS with either gefitinib (n=94; median, 10.5 months) or erlotinib treatment (n=52; median, 10.4 months). In conclusion, PFS showed no difference with either agent in patients whose tumors had EGFR-activating mutations, but was significantly longer in patients whose tumors did not have EGFR-activating mutations when receiving erlotinib treatment. IntroductionWorldwide, lung cancer is the leading cause of cancer mortality (1). Major progression in understanding molecular cancer biology and in determining the mechanisms of oncogenesis during the last decade has resulted in the development of molecular targets for non-small cell lung cancer (NSCLC) treatments. Inhibition of the epidermal growth factor receptor (EGFR) pathway with tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, provides an effective and promising treatment for NSCLC, as either first-line or salvage therapy, with the added advantage of improved efficacy, tolerability and quality of life compared with other chemotherapy agents (2-9). It has been demonstrated that a subset of patients (female, never smoked, East Asian with an adenocarcinoma diagnosis) may respond better to EGFR-TKIs. A higher prevalence of sensitive EGFR-activating mutations (deletion in exon 19 or point mutation of L858R in exon 21) has been found in this subset of patients (10-12).Gefitinib and erlotinib were each compared with a placebo in phase III randomized trials (ISEL and BR.21, respectively) in which the majority of enrolled patients were Caucasian (2,3). The varying overal...

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confidence: 70%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations

Chen

Tsai

et al. 2011

Experimental and Therapeutic Medicine

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“…EGFR mutations are commonly associated with female gender, adenocarcinoma histology, never-smoker status and Asian ethnicity (9,13,14,(18)(19)(20)(21). Therefore, these characteristics have been integrated into clinical practice to guide treatment selection for patients with advanced lung cancer (13,14,(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Hsiao¹,

Lin

Chou

et al. 2013

Molecular and Clinical Oncology

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Abstract. Mutations in epidermal growth factor receptor (EGFR) commonly occur in non-small-cell lung cancer (NSCLC) patients characterized by female gender, never-smoker status and adenocarcinoma histology. The aim of this study was to determine whether gender is a confounding factor for EGFR mutations in NSCLC. To elucidate the confounding effect, Pearson's χ 2 test and logistic regression models were used to correlate these characteristics with EGFR mutations in 426 NSCLC patients treated at our institutes. Of those 426 NSCLC patients, 47% were females, 57% were non-smokers and 84% had adenocarcinomas. The multivariate logistic regression analysis demonstrated that never-smoker status [odds ratio (OR)=3.49, 95% confidence interval (CI): 1.99-6.13; P<0.001)] and adenocarcinoma (OR=9.43, 95% CI 3.62-24.56; P<0.001) were associated with EGFR mutations; however, gender was not (OR=1.25, 95% CI: 0.73-2.15; P=0.416). Furthermore, gender was not associated with EGFR mutation subtypes (OR=1.19, 95% CI: 0.56-2.50; P=0.650). The frequency of EGFR mutations among females and males was not different in non-smokers (64.8 vs. 55.8%, P=0.204) or ever-smokers (27.8 vs. 24.2%, P=0.775). Therefore, if the assessment for EGFR mutation status was limited to non-smoking females with adenocarcinoma, up to 40% of the patients harboring EGFR mutations would be precluded from the benefit of EGFR inhibitor therapy. Our results indicated that gender is a confounding factor for EGFR mutations in NSCLC and suggested that gender may not be associated with tumorigenesis in NSCLC-harboring EGFR mutations.

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“…According to clinical trials which directly compared between these two drugs, however, there were no significant differences 6,8 . In Taiwan, there were contradictory reports that erlotinib has an excellent profile of the DCR, the PFS and the OS 23 . Further studies are therefore warranted to examine the difference in the treatment effect between the two drugs.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Therapeutic Efficacy of Gefitinib and Erlotinib in Patients with Squamous Cell Lung Cancer

et al. 2011

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Background: Gefitinib and erlotinib are useful, molecular targeted agents in patients with non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. We compared the efficacy and toxicity of two drugs in patients with squamous cell lung cancer, most of whom are male smokers. Methods: We retrospectively reviewed the clinical information on patients with NSCLC who were treated with gefitinib or erlotinib treatment at Chonnam National University Hwasun Hospital between July 2002 and November 2009. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were compared between the two drugs. Results: A total of 182 (100 gefitinib vs. 82 erlotinib) of 584 patients treated by targeted agents had squamous histology. Of the 182 patients, 167 (91.7%) were male and 159 (87.4%) were smokers. The ORR and disease control rate (DCR) were 4.9% and 40.6%, and there was no significant difference between gefitinib and erlotinib (ORR, 5.0% vs 4.8%; p=0.970; DCR, 40.0% vs 41.4%; p=0.439). The median OS in the gefitinib group was 12.1 months, and that in the erlotinib was 12.7 months (hazard ratio [HR], 1.282; 95% confidence interval [CI], 0.771∼2.134; p=0.339). The median PFS for the gefitinib group was 1.40 months, compared with 1.37 months for the erlotinib group (HR, 1.092; 95% CI, 0.809∼1.474; p=0.564). Skin rash ≥grade 3 was more common in erlotinib (12.2%) than gefitinib (1.0%, p=0.003) groups. Conclusion: This retrospective study showed that the two drugs appear to have similar antitumor efficacy and toxicity except for skin rash.

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Different Efficacies of Erlotinib and Gefitinib in Taiwanese Patients with Advanced Non-small Cell Lung Cancer: A Retrospective Multicenter Study

Abstract: Taiwanese patients with advanced NSCLC treated with erlotinib reported higher disease control rate, longer progression-free survival, and overall survival compared with patients treated with gefitinib.

Cited by 25 publications

References 33 publications

Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations

Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer

Comparison of Therapeutic Efficacy of Gefitinib and Erlotinib in Patients with Squamous Cell Lung Cancer

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