Survival difference between EGFR Del19 and L858R mutant advanced non-small cell lung cancer patients receiving gefitinib: a propensity score matching analysis

Zhuo, Minglei; Zheng, Qiwen; Zhao, Jun; Wu, Meina; An, Tongtong; Wang, Yuyan; Li, Jianjie; Wang, Shuhang; Zhong, Jia; Yang, Xue; Chen, Hanxiao; Jia, Bo; Dong, Zhi Wei; Gao, Emei; Wang, Jingjing; Wang, Ziping

doi:10.21147/j.issn.1000-9604.2017.06.10

Cited by 11 publications

(11 citation statements)

References 22 publications

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“…As expected, both survival indices were better for patients with T790M-mediated resistance, reflecting the slow-growing nature of T790M-positive lung cancer (Figure 5, C and D ). In multivariate Cox analysis (Supplemental Figures 2 and 3), the poor prognostic factors, which had statistically significant effects on OS, were male sex [HR = 1.65, 95% CI 1.07-2.56, P = .03] and stage IVb [HR = 3.02, 95% CI 1.47-6.24, P < .01], whereas the types of EGFR mutation did not affect survival (Figure 5 and Supplemental Figure 3), which was also observed in another recent study using propensity score matching [25].…”

Section: Discussionsupporting

confidence: 73%

Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis

Yoon

Kim

Lee

et al. 2019

Translational Oncology

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Afatinib, a second-generation, irreversible pan-HER inhibitor, shows better suppression of T790M-positive lung cancer cells than gefitinib in preclinical studies. However, whether the effect of afatinib on T790M acquisition differs from that of gefitinib when used clinically as first-line therapy remains unclear. To reaffirm the preclinical efficacy of afatinib on T790M-positive lung cancer cells, H1975 cells and established PC-9 cells resistant to gefitinib and erlotinib by T790M were used. In total, 398 patients with second biopsy at progression with stage IIIB/IV non–small cell lung cancer with EGFR mutation, treated with afatinib or gefitinib as first-line therapy, were retrospectively reviewed. Propensity score matching was used to balance covariates. Afatinib inhibited the growth of lung cancer cells with low T790M allele frequencies, which are resistant to gefitinib, but not those with high T790M allele frequencies. Afatinib and gefitinib showed similar efficacy in terms of progression-free survival (PFS) (11.5 vs 13.4 months, P = .08) and overall survival (OS) (29.3 vs 28.5 months, P = .76). T790M patients had better PFS and OS than those without T790M. There was no significant difference in the cumulative T790M acquisition ratio over time between afatinib and gefitinib (48.8% vs 59.3%, P = .317). The median time to acquire T790M was 12.9 months for afatinib and 15.7 months for gefitinib ( P = .342). Although afatinib inhibited the growth of lung cancer cells with low T790M allele frequencies in preclinical studies, this could not be translated into clinical efficacy in terms of lowering the rate or delaying the time of T790M acquisition.

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Section: Discussionsupporting

confidence: 73%

Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis

Yoon

Kim

Lee

et al. 2019

Translational Oncology

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“…Our findings provided further evidence that EGFR gene mutation varied by clinicopathological features which showed some predictors for EGFR gene mutation. So far, the results of survival difference between Del19 and L858R subtypes were still inconsistent 19. In our study, the survival time of exon 18 group was statistically lower than that of exon 19 group and exon 21 group, but the survival time between exon 19 group and exon 21 group was not statistically different, suggesting there were no differences in the survival time of Del19 and L858R subtypes in the patients with lung adenocarcinoma, which needed to be further investigated.…”

Section: Discussioncontrasting

confidence: 51%

<p>Prognostic analysis of patients with mutant and wild-type <em>EGFR</em> gene lung adenocarcinoma</p>

Zheng

Zhang

Zhan

et al. 2019

CMAR

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Purpose The purpose of this study was to investigate the relationship between epidermal growth factor receptor ( EGFR ) gene mutation and clinicopathological features of lung adenocarcinoma, and the prognostic and therapeutic value of EGFR . Methods EGFR gene mutations were detected in 424 patients with lung adenocarcinoma by amplification refractory mutation system (ARMS). Results The total EGFR gene mutation rate was 55.2% (234/424) and EGFR gene mutation rates were statistically different in gender, smoking status, and pathological degree ( P <0.05). The overall survival (OS) time of lung adenocarcinoma patients with mutation of exon 18 was lower than those with mutation of exon 19 and exon 21 (both P <0.05), but no significant difference was seen between those with mutation of exon 19 and exon 21 ( P >0.05). Among 424 cases of lung adenocarcinoma, multivariate analysis showed that EGFR gene mutation, age, gender, clinical stages, and pathological degree ( P <0.05) were statistically significant prognostic factors. In multivariate analysis, prognostic factors of patients with EGFR gene mutation were associated with EGFR-TKI treatment, surgery treatment, pathological degree, clinical stages, and age ( P <0.05), whereas in patients without EGFR gene mutation, prognostic factors were related to surgery treatment, pathological degree, clinical stages, gender, age, and smoking status ( P <0.05). Conclusion The OS time of patients with mutation of exon 18 was lower than those of exon 19 and exon 21. EGFR-TKI treatment was an independent positive predictor in patients with EGFR gene mutation. Surgery treatment, age, clinical stages, and pathological degree were independent prognostic factors in Chinese patients with lung adenocarcinoma no matter whether with EGFR gene mutation or not.

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“…Many groups have explored whether initial EGFR ‐activating mutation subtypes might serve as a prognostic factor for TKI treatment and possible TKI resistance with T790M mutation (Deng et al ., ; Ma et al ., ; Matsuo et al ., ; O'Kane et al ., ; Zhuo et al ., ). Recently, a meta‐analysis by Wu group suggested that tumors harboring EGFR 19del had a higher T790M mutation rate than those having L858R (Deng et al ., ).…”

Section: Discussionmentioning

confidence: 98%

Combined plasma and tissue genotyping of EGFR T790M benefits NSCLC patients: a real‐world clinical example

Wei

Zhao

et al. 2019

Molecular Oncology

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Acquired resistance to epidermal growth factor receptor ( EGFR )‐tyrosine kinase inhibitors ( TKI s) is a prevalent clinical problem in the management of advanced non‐small‐cell lung cancer ( NSCLC ) with TKI ‐sensitizing mutations in the EGFR gene. Third‐generation EGFR ‐ TKI s have demonstrated potent activity against TKI resistance mediated by the EGFR T790M mutation, and standard rebiopsy and liquid biopsy are utilized to assess the T790M status of the NSCLC patients who experienced progressive disease (PD). Here, we conducted a retrospective study to assess 375 patients whose initial biopsy indicated a TKI ‐sensitizing mutation (either EGFR 19del or L858R) and who developed PD after treatment with first‐generation TKI s, and assayed for T790M status. We adopted a combination approach in which tissue rebiopsy is preferred, utilizing liquid biopsies when tissue rebiopsy is not feasible. We analyzed the potential predictive clinical factors affecting T790M detection, evaluated the standard rebiopsy and liquid biopsy methods in T790M genotyping, and reported the clinical performance of osimertinib. Our results suggested that primary EGFR 19del, brain metastasis, and longer progression‐free survival of initial EGFR ‐ TKI treatment are associated with acquired T790M resistance. T790M‐positive patients significantly benefited from osimertinib. In conclusion, the real‐world clinical adoption of the combination approach with both tissue rebiopsy and liquid biopsy for T790M genotyping may provide significant benefits to patients who have developed PD after first‐generation TKI treatments.

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Survival difference between EGFR Del19 and L858R mutant advanced non-small cell lung cancer patients receiving gefitinib: a propensity score matching analysis

Abstract: No significant difference was found in the PFS or OS between the Del19 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Del19 and L858R groups. PSM is of important value to the elimination of potential bias.

Cited by 11 publications

References 22 publications

Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis

Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis

<p>Prognostic analysis of patients with mutant and wild-type <em>EGFR</em> gene lung adenocarcinoma</p>

Combined plasma and tissue genotyping of EGFR T790M benefits NSCLC patients: a real‐world clinical example

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