Distinct Benefit of Overall Survival between Patients with Non-Small-Cell Lung Cancer Harboring &lt;b&gt;&lt;i&gt;EGFR&lt;/i&gt;&lt;/b&gt; Exon 19 Deletion and Exon 21 L858R Substitution

Koyama, Nobuyuki; Watanabe, Yasutaka; Iwai, Yasuhiro; Kawamura, Rumi; Miwa, Chihiro; Nagai, Yoshinori; Hagiwara, Koichi; Koyama, Shinichiro

doi:10.1159/000454944

Cited by 18 publications

(5 citation statements)

References 33 publications

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“…Although our small sample size may have reduced the statistical power of the OS comparison, this is nevertheless in concordance with findings from Peking University Cancer Hospital [19] . In contrast, EGFR-TKIs provided a significant OS benefit to patients harboring 19 del compared with L858R mutations as reported in another study [20] . In our study, the OS of patients with L858R mutations was longer than that of patients with EGFR 19 del (26.5 months).…”

Section: Discussionmentioning

confidence: 63%

Treatment and survival status of patients with EGFR mutation-positive stage IV lung adenocarcinoma: five-year follow-up results in the Ordos Area of Inner Mongolia, China*

Jin¹,

Wang²,

Shu-qin³

et al. 2018

Oncology and Translational Medicine

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ObjectiveWe aimed to determine the epidermal growth factor receptor (EGFR) mutation status and treatment survival of patients with stage IV lung adenocarcinoma living in the Ordos area of Inner Mongolia, China.MethodsEGFR testing and first-line tyrosine kinase inhibitor (TKI) treatment rates of patients with stage IV lung adenocarcinoma were analyzed from June 2012 to June 2016. Kaplan-Meier survival curves were constructed to compare patients who received different treatment strategies and those harboring different EGFR mutation statuses.ResultsEGFR testing and mutation rates were 65.60% and 52.90%, respectively, and improved continuously from June 2012 to June 2016. Among patients with EGFR mutations, 38.9% had EGFR 19 del, 48.2% had L858R, 4.2% had co-existing mutations in exons 19 and 21, and 8.4% had uncommon mutations. The median overall survival (OS) was 29.5, 26.5, and 16.0 months for patients receiving both TKI and chemotherapy, TKI alone, and chemotherapy alone, respectively (P = 0.047). The OS was 26.5 and 30.0 months for patients harboring EGFR 19 del and L858R mutations, respectively (P = 0.096).ConclusionThe high OS rates of stage IV lung adenocarcinoma patients living in the Ordos area may be attributed to continuous improvements in EGFR testing and first-line TKI treatment rates. In the era of TKIs, chemotherapy for increasing OS times should be emphasized.

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Section: Discussionmentioning

confidence: 63%

Treatment and survival status of patients with EGFR mutation-positive stage IV lung adenocarcinoma: five-year follow-up results in the Ordos Area of Inner Mongolia, China*

Jin¹,

Wang²,

Shu-qin³

et al. 2018

Oncology and Translational Medicine

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“…Del19 and L858R mutations in EGFR have different predictive and prognostic impacts. [ 34 , 35 ] In a combined analysis of the Lux-lung 3 and 6 trials investigating afatinib versus chemotherapy, overall survival was improved in patients with the Del19 mutation but not in patients with the L858R mutation. [ 26 ] However, utilizing the del19 mutation to guide treatment decisions has not yet gained solid supporting evidence.…”

Section: Discussionmentioning

confidence: 99%

A network meta-analysis of nonsmall-cell lung cancer patients with an activating EGFR mutation

Lin

Ma²,

Wu³

et al. 2018

Medicine

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Background:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line treatment for nonsmall-cell lung cancer (NSCLC) patients with an activating EGFR mutation. Osimertinib, compared with erlotinib or gefitinib, showed an improvement in progression-free survival (PFS) in a recent trial. The authors compared EGFR TKIs in terms of PFS in a network meta-analysis.Methods:The PubMed and Embase databases and meeting abstracts were screened for relevant studies between January 2009 and November 2017. A random-effect frequentist network meta-analysis model was conducted to assess PFS. P-score was used to rank treatment effects.Results:Eleven trials with 3145 patients and 5 TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) were included. Heterogeneity and inconsistency existed in the network analysis. Gefitinib and erlotinib had similar effects (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.76–1.15). For all patients, the 3 TKIs with the highest probability of benefit were osimertinib, dacomitinib, and afatinib, with P-scores of 91%, 78%, and 46%, respectively. Compared with erlotinib or gefitinib, osimertinib was associated with improvement in men (HR = 0.79, 95% CI, 0.68–0.92), non-Asians (HR = 0.63, 95% CI, 0.40–0.98), smokers (HR = 0.73, 95% CI, 0.56–0.95), and those with a Del19 mutation (HR = 0.69, 95% CI, 0.54–0.90); dacomitinib and afatinib showed no improvement. Toxicity profiles mostly overlapped in all the EGFR TKIs. Toxicity-related death was rare.Conclusions:Osimertinib was shown to be the best agent to achieve the longest PFS in NSCLC patients with an activating EGFR mutation. However, the benefit of osimertinib might be restricted to certain subgroups.

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“…36 It has been reported that NSCLC patients harboring EGFR 19del and 21L858R mutations present diverse biological profiles, clinical features and prognoses, 37 and previous studies have demonstrated various responses to first-generation EGFR-TKIs between NSCLC patients harboring EGFR 19del and 21L858R mutations. [38][39][40][41][42][43][44] Results from a meta-analysis of 22 eligible trials involving 1082 patients showed that advanced NSCLC patients harboring EGFR 19del mutations had longer OS and PFS than those with 21L858R mutations, 45 which may be explained partly by the higher proportion of the EGFR T790M mutation in patients with EGFR 19del mutations. 46 However, the exact mechanisms responsible for the difference in the responses to EGFR-TKIs between advanced NSCLC patients with EGFR 19del and 21L858R mutations remain to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of First-Generation EGFR-TKIs Combined with Chemotherapy for Treatment-Naïve Advanced Non-Small-Cell Lung Cancer Patients Harboring Sensitive EGFR Mutations: A Single-Center, Open-Label, Single-Arm, Phase II Clinical Trial

Lin¹,

Li²,

Chen³

et al. 2021

JIR

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Purpose This single-center, open-label, single-arm, phase II clinical trial aimed to examine the efficacy and safety of the first-generation EGFR-TKIs combined with chemotherapy among treatment-naïve advanced non-small-cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. Materials and Methods Patients with advanced EGFR -mutant NSCLC were given concurrent gefitinib (250 mg orally daily) and 3-week cycle of carboplatin plus pemetrexed for 4 to 6 cycles, followed by gefitinib maintenance until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This trial was registered at ClinicalTrials.gov (NCT02886195). Results Of the 21 patients enrolled in this study, a 76.2% ORR and 100% DCR were observed and a higher ORR was seen in patients with EGFR 21L858R mutations than in those with 19del mutations ( P = 0.012). The subjects had a median PFS of 15.0 months and a median OS of 26.0 months, and numerically longer PFS was seen in patients with EGFR 21L858R mutations than in those with 19del mutations ( P = 0.281). There were 15 NSCLC patients without cerebral metastases at baseline, with 4 cases developing cerebral metastases during the treatment, and the 6-, 12- and 24-month cumulative incidence rates of the central nervous system metastasis were 6.67%, 13.3% and 26.7%, respectively. There were 17 subjects with progressive diseases tested for EGFR T790M mutations, and 11 cases were positive for T790M mutations. Grade 3 toxicity included neutropenia (9.5%), leukopenia (4.8%), liver dysfunction (9.5%) and diarrhea (4.8%), and no grade 4 adverse events or treatment-related death occurred. Conclusion The combination of first-generation EGFR-TKIs and chemotherapy achieves a satisfactory PFS, ORR and DCR and well-tolerated toxicity in advanced NSCLC patients with EGFR mutations, notably in patients with EGFR L858R mutations.

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Distinct Benefit of Overall Survival between Patients with Non-Small-Cell Lung Cancer Harboring <b><i>EGFR</i></b> Exon 19 Deletion and Exon 21 L858R Substitution

Cited by 18 publications

References 33 publications

Treatment and survival status of patients with EGFR mutation-positive stage IV lung adenocarcinoma: five-year follow-up results in the Ordos Area of Inner Mongolia, China*

Treatment and survival status of patients with EGFR mutation-positive stage IV lung adenocarcinoma: five-year follow-up results in the Ordos Area of Inner Mongolia, China*

A network meta-analysis of nonsmall-cell lung cancer patients with an activating EGFR mutation

Efficacy and Safety of First-Generation EGFR-TKIs Combined with Chemotherapy for Treatment-Naïve Advanced Non-Small-Cell Lung Cancer Patients Harboring Sensitive EGFR Mutations: A Single-Center, Open-Label, Single-Arm, Phase II Clinical Trial

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