Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival

Lee, Chee Khoon; Davies, Lucy; Wu, Yi‐Long; Mitsudomi, Tetsuya; Inoue, Akira; Rosell, Rafael; Zhou, Caicun; Nakagawa, Kazuhiko; Thongprasert, Sumitra; Fukuoka, Masahiro; Lord, Sarah J.; Marschner, Ian C.; Tu, Yu–Kang; Gralla, Richard J.; Gebski, Val; Mok, Tony; Yang, James Chih Hsin

doi:10.1093/jnci/djw279

Cited by 208 publications

(195 citation statements)

References 24 publications

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“…A recent meta-analysis of first line trials of gefitinib or erlotinib vs. chemotherapy showed that 34% of the patients with EGFR TKI did not receive any subsequent treatment after progression. 23 In our study, very few patients switched or got rechallenged on EGFR TKIs, mainly because during that time no EGFR TKIs (osimertinib) were available as a second line treatment option for patients who had developed the T790M resistance mutation after first line treatment. 28 Unfortunately, we did not have access to drugs dispensed to individuals during a hospital stay (e.g., chemotherapy or radiotherapy), creating observation gaps which is likely to have an impact on survival outcome.…”

Section: Discussionmentioning

confidence: 89%

“…The EURTAC trial, 10 enrolled a European patient population with advanced EGFR mutation positive NSCLC, reported OS of 22.9 months for patients treated with Erlotinib first-line treatment. 23 In this trial, the patients had no history of chemotherapy for metastatic disease, median age 65 years, 67% were female and 95% had adenocarcinoma. While patients in our study were older (mean age 67 years), fewer females (59%) and fewer adenocarcinoma (85%).…”

Section: Discussionmentioning

confidence: 94%

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Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010–2016 in Sweden: A nationwide observational study

Bergqvist

Christensen

Wiklund

et al. 2019

Intl Journal of Cancer

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The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB–IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010–2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient‐, tumor‐related factors with OS. Of 9,992 Stage IIIB–IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less ≥1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non‐TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010–2011; 14.4 months 2012–2013; 18.6 months 2014–2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 94%

Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010–2016 in Sweden: A nationwide observational study

Bergqvist

Christensen

Wiklund

et al. 2019

Intl Journal of Cancer

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“…A meta‐analysis of randomized controlled trials (RCTs) suggested that EGFR‐mutated NSCLC patients treated with first‐line first‐generation EGFR‐TKI (gefitinib or erlotinib) therapy had longer median progression‐free survival (PFS) than chemotherapy‐treated patients (11.0 vs . 5.6 months) . Treatment with the second‐generation EGFR‐TKI afatinib, which irreversibly inhibits EGFR and other ErbB family targets, significantly improved the PFS of untreated EGFR‐mutated patients compared to chemotherapy (11.1 vs .…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of osimertinib in treating EGFR‐mutated advanced NSCLC: A meta‐analysis

Fan

Qian

et al. 2019

Intl Journal of Cancer

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Osimertinib is the only Food and Drug Administration‐approved third‐generation epidermal growth factor receptor (EGFR) tyrosine‐kinase inhibitor (TKI). A meta‐analysis was performed to aggregate the mixed results of published clinical trials to assess the efficacy and safety of osimertinib. A systematic search of the PubMed, Web of Science, and Cochrane Library electronic databases was performed to identify eligible literature. The primary endpoints were overall response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and adverse events (AEs). A total of 3,086 advanced nonsmall cell lung cancer (NSCLC) patients from 11 studies have been identified. The aggregate efficacy parameters for treatment‐naïve patients with EGFR‐TKI‐sensitizing mutations are as follows: ORR 79% (95% CI 75–84%), DCR 97% (95% CI 95–99%), 6‐month PFS 83% (95% CI 80–87%), and 12‐month PFS 64% (95% CI 59–69%). The aggregate efficacy parameters for advanced NSCLC harboring T790M mutations after earlier‐generation EGFR‐TKI therapy are as follows: ORR 58% (95% CI 46–71%), DCR 80% (95% CI 63–98%), 6‐month PFS 63% (95% CI 58–69%), and 12‐month PFS 32% (95% CI 17–47%). EGFR‐TKI‐naïve patients with EGFR‐positive mutations tend to have longer median PFS than EGFR‐TKI‐pretreated counterparts (19.17 vs . 10.58 months). The most common AEs were diarrhea and rash, of which the pooled incidences were 44 and 42%, respectively. Generally, osimertinib is a favorable treatment option for previously treated T790M mutation‐positive advanced NSCLC as well as a preferable therapy for untreated EGFR mutation‐positive advanced NSCLC. Additionally, osimertinib is well tolerated by most patients.

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“…Patients with advanced disease have lost the opportunity of surgery and thus are treated by chemoradiation or targeted therapy. At present, the most commonly used target drugs for NSCLC treatment are EGFR‐tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib . However, not all NSCLC patients can benefit from EGFR‐TKI treatment.…”

Section: Introductionmentioning

confidence: 99%

Relationship between EGFR mutation and computed tomography characteristics of the lung in patients with lung adenocarcinoma

2018

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BackgroundThe aim of this study was to investigate the relationship between EGFR mutation and computed tomography (CT) features in patients with adenocarcinoma of the lung.MethodsOne hundred and ninety two lung adenocarcinoma patients who underwent surgery were retrospectively included in this study. Examination of EGFR gene mutation was performed on all resected tumor samples. The 192 recruited lung adenocarcinoma patients were divided into groups according to EGFR mutation status: patients with mutations in exons 18–21 (effective mutated, n = 61) and non‐mutated (n = 131). The clinical characteristics and lung CT imaging features of the two groups were recorded and compared. Univariate and logistic regression analysis were performed to identify the independent risk factors relevant to effective EGFR gene mutation.ResultsThe independent risk factors relevant to effective EGFR mutation were evaluated by logistic regression test. The results indicated that female gender (odds ratio [OR] 3.23), lung CT features of lymphangitis carcinomatosa (OR 2.66), semi‐solid lesion density (OR 3.56), and spicule sign (OR 1.61) were independent risk factors relevant to EGFR mutation.ConclusionFemale patients with lung CT features of lymphangitis carcinomatosa, semi‐solid lesion density, and spicule sign are more prone to harbor EGFR gene mutations and are more likely to benefit from targeted therapy.

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Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival

Abstract: Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.

Cited by 208 publications

References 24 publications

Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010–2016 in Sweden: A nationwide observational study

Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010–2016 in Sweden: A nationwide observational study

Efficacy and safety of osimertinib in treating EGFR‐mutated advanced NSCLC: A meta‐analysis

Relationship between EGFR mutation and computed tomography characteristics of the lung in patients with lung adenocarcinoma

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