Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L

Urata, Yoshiko; Katakami, Nobuyuki; Morita, Satoshi; Kaji, Ryuji; Yoshioka, Hiroshige; Seto, Takashi; Satouchi, Miyako; Iwamoto, Yasuo; Kanehara, Masashi; Fujimoto, Daichi; Ikeda, Norihiko; Murakami, Haruyasu; Daga, Haruko; Oguri, Tetsuya; Goto, Isao; Imamura, Fumio; Sugawara, Shunichi; Sasaki, Hideo; Nogami, Naoyuki; Negoro, Shunichi; Nakagawa, Kazuhiko; Nakanishi, Yoichi

doi:10.1200/jco.2015.63.4154

Cited by 135 publications

(123 citation statements)

References 16 publications

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“…Zhang et al also showed that the patients with the exon 19 deletion in EGFR receiving first-line EGFR-TKIs had longer PFS than those with exon 21 substitution (16). Similarly, Urata et al identified patients with the EGFR exon 19 deletion subgroup had slightly longer PFS when treated with gefitinib and erlotinib than those with p.Leu858Arg mutation (14). Furthermore, analysis of two phase III trials, LUX-Lung 3 and LUX-Lung 6, indicated that the first-line afatinib compared to chemotherapy improved OS for patients with the EGFR exon 19 deletion but not for patients with p.Leu858Arg substitution (17).…”

Section: Univariate Analysis Multivariate Analysis Median Pfs -------mentioning

confidence: 94%

“…The authors concluded that the reason for treatment failure was including patients with unknown EGFR gene mutations with at least two out of three clinical factors associated with a higher incidence of EGFR gene mutations (6). Similarly, in a recent randomized phase III study of 562 pretreated patients with lung adenocarcinoma (including 401 with EGFR mutations), the response rates were 44 and 46% and the median PFS was 7.5 and 6.5 months in erlotinib-and gefitinib-treatment arms, respectively (14). The first head-to-head comparison of afatinib and gefitinib was recently reported in the prospective phase IIb LUX-Lung 7 clinical trial (7).…”

Section: Univariate Analysis Multivariate Analysis Median Pfs -------mentioning

confidence: 97%

“…Urata et al found no significant difference in the PFS among patients with the EGFR p.Leu858Arg mutation (n=172), the EGFR exon 19 deletion (n=192), or those with rare EGFR mutations (n=25) who were treated with gefitinib and erlotinib (14). Zhang et al also showed that the patients with the exon 19 deletion in EGFR receiving first-line EGFR-TKIs had longer PFS than those with exon 21 substitution (16).…”

Section: Univariate Analysis Multivariate Analysis Median Pfs -------mentioning

confidence: 99%

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Comparison of the effectiveness of erlotinib, gefitinib, and afatinib for treatment of non-small cell lung cancer in patients with common and rare EGFR gene mutations

et al. 2017

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Abstract. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are routinely used to treat non-small cell lung cancer (NSCLC) in patients with common activating mutations of the EGFR gene. The aim of the study was to compare the efficacies of EGFR-TKIs in patients with common (exon 19 deletions and exon 21 p.Leu858Arg) and rare EGFR mutations. A retrospective analysis of 180 NSCLC patients with common (n=167) and rare (n=13) EGFR mutations treated with erlotinib (n=98), gefitinib (n=66) and afatinib (n=16) was performed. EGFR mutations were determined using RT-PCR and the EntroGen EGFR Mutations Analysis kit. Partial and complete response (PR and CR), progression-free survival (PFS), and overall survival (OS) were analyzed. Demographic and clinical factors had no impact on PFS or OS in patients treated with EGFR-TKIs. Erlotinib, gefitinib, and afatinib showed similar efficacies based on treatment response, median PFS, and OS. The type of EGFR mutation had no impact on median OS; however, median PFS was significantly longer in patients with the exon 19 deletion compared to patients with the exon 21 p.Leu858Arg substitution and rare EGFR gene mutations (P=0.013). Patients with common EGFR mutations showed significantly longer median PFS than those with rare EGFR mutations (10 vs. 5 months; P=0.009). Erlotinib, gefitinib, and afatinib show similar efficacies in NSCLC patients with both common and rare EGFR mutations. When undergoing EGFR-TKI treatment, patients with rare EGFR mutations showed similar OS but poorer PFS. Further investigation into the associations between particular rare EGFR mutations and EGFR-TKIs treatment outcomes is required.

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Section: Univariate Analysis Multivariate Analysis Median Pfs -------mentioning

confidence: 94%

Section: Univariate Analysis Multivariate Analysis Median Pfs -------mentioning

confidence: 97%

Section: Univariate Analysis Multivariate Analysis Median Pfs -------mentioning

confidence: 99%

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Comparison of the effectiveness of erlotinib, gefitinib, and afatinib for treatment of non-small cell lung cancer in patients with common and rare EGFR gene mutations

et al. 2017

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“…In the randomized phase III trial of Urata and colleagues comparing gefitinib and erlotinib in previously treated adenocarcinoma, the number of patients who discontinued treatment due to toxicity was similar (33 and 32 patients, respectively) [Urata et al 2016]. As reported in previous trials, grade 3-4 rash toxicities were more frequent for erlotinib (18.1%) than for gefitinib (2.2%), whilst ALT/AST elevation was more common for gefitinib (6.2/13% for gefitinib versus 2.2/3.3% for erlotinib).…”

Section: Is There Evidence Of Different Efficacy Between Egfr Tkis Fomentioning

confidence: 96%

“…There have been two studies conducted in Asian patients which directly compared erlotinib and gefitinib, but were based on previously treated patients [Yang et al 2015c;Urata et al 2016]. Neither of these studies showed differences in PFS and OS between TKIs.…”

Section: Is There Evidence Of Different Efficacy Between Egfr Tkis Fomentioning

confidence: 99%

Treatment choice in epidermal growth factor receptor mutation-positive non-small cell lung carcinoma: latest evidence and clinical implications

Juan

Popat

2017

Ther Adv Med Oncol

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Discovery of sensitizing mutations in epidermal growth factor receptor (EGFR) and the subsequent development of EGFR tyrosine kinase inhibitors (TKIs) have substantially changed the treatment of lung cancer. First-line treatment with EGFR TKIs (gefitinib, erlotinib and afatinib) has demonstrated a superior response rate and progression-free survival (PFS) compared with chemotherapy in EGFR-mutation positive patients. However, a number of open questions remain, such as choice between the three EGFR TKIs licensed, treatment of patients unsuitable for chemotherapy due to morbidity or advanced age, management of acquired resistance and optimal biological sample to determine EGFR status. Recently the first headto-head trial comparing gefitinib and afatinib (LUX-Lung 7) has been reported. Moreover, third-generation EGFR TKIs such as osimertinib, rociletinib, olmutinib and ASP8273, with preferential activity against T790M mutant tumours, the commonest resistance mechanism to EGFR TKIs, have shown promising results in early clinical trials, with osimertinib now licensed. In this review, we summarize latest advances in the treatment of EGFR-mutation positive patients focusing on controversial areas and emerging challenges to optimally treat these patients in the future.

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Misleading Reporting (Spin) in Noninferiority Randomized Clinical Trials in Oncology With Statistically Not Significant Results

et al. 2021

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Key Points Question Is the interpretation and reporting of noninferiority trials with primary end point results that are not statistically significant correct, and what are the associated factors of misleading reporting? Findings This systematic review of 52 noninferiority randomized clinical trials of cancer treatments with results for primary end points that are not statistically significant, 75% included misleading reporting. Multivariable analysis found that the prevalence of misleading reporting was significantly lower in reports with funding from for-profit sources and higher in reports of novel experimental treatments. Meaning These findings suggest that authors should carefully consider noninferiority cancer clinical trial result interpretation and reporting, especially for primary outcome results that are not statistically significant.

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Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L

Abstract: The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria.

Cited by 135 publications

References 16 publications

Comparison of the effectiveness of erlotinib, gefitinib, and afatinib for treatment of non-small cell lung cancer in patients with common and rare EGFR gene mutations

Comparison of the effectiveness of erlotinib, gefitinib, and afatinib for treatment of non-small cell lung cancer in patients with common and rare EGFR gene mutations

Treatment choice in epidermal growth factor receptor mutation-positive non-small cell lung carcinoma: latest evidence and clinical implications

Misleading Reporting (Spin) in Noninferiority Randomized Clinical Trials in Oncology With Statistically Not Significant Results

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