First-line Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor Treatment Research Articles

Outcomes in non-small cell lung cancer with uncommon epidermal growth factor receptor L858 substitutions under first-line epidermal growth factor receptor tyrosine kinase inhibitors: A large real-world cohort study.

Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFRL858R mutation caused by c.2573 T > G, have been identified in non-small cell lung cancer (NSCLC), yet their genomic features and survival benefits with EGFR tyrosine kinase inhibitor (TKI) treatment have not been fully explored. We retrospectively enrolled 489 NSCLC patients with baseline tumor tissue/plasma samples carrying uncommon EGFRL858R (N = 124), EGFRL858Q/M (N = 17), or classical EGFRL858R mutations (N = 348). The comparison of molecular features was performed using treatment-naïve tumor tissues. Survival benefits and resistance mechanisms of first-line EGFR TKI treatment were studied in an advanced disease subcohort. NSCLCs harboring uncommon EGFRL858R had lower TP53 mutation prevalence (p = 0.04) and chromosome instability scores (p = 0.02) than those with classical EGFRL858R. Concomitant EGFRL861Q mutations were enriched in NSCLCs with EGFRL858Q/M (p < 0.01), with cooccurrence in those carrying EGFRL858M. Patients with uncommon EGFRL858R experienced improved progression-free survival (PFS) compared to those with classical EGFRL858R (median: 13.0 vs. 10.0 months, hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.41-0.80). The association remained significant when adjusting for sex, age, histological subtype, TKI category, and anti-vascular therapy (HR: 0.55, 95% CI: 0.39-0.77). Furthermore, EGFRL858Q/M patients showed enhanced first-line PFS (vs. classical EGFRL858R, HR: 0.26, 95% CI: 0.10-0.67), potentially benefiting more from afatinib. Additionally, NSCLCs with uncommon EGFRL858R and classical EGFRL858R had similar resistance profiles to EGFR TKIs. In conclusion, NSCLCs carrying atypical EGFR L858 aberrations, which had fewer TP53 mutations and higher chromosome stability, exhibited improved PFS under first-line EGFR TKIs than those with the classical EGFRL858R.

A Meta-analysis of Randomised Controlled Trials Comparing Combination Therapy as Second-line Treatment With Monotherapy in Advanced Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutation.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR mutation; however, resistance is common. Combinatorial strategies have been explored to improve survival. This meta-analysis assesses the efficacy and safety of combination therapy versus monotherapy in patients with advanced NSCLC who failed first-line EGFR-tyrosine kinase inhibitor treatment. We searched randomized controlled trials from PubMed, Web of Science, Google Scholar, Cochrane Library, and ClinicalTrial.gov. The efficacy and toxicity of combination treatment groups were assessed in terms of progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis included 6 randomized controlled trials covering 785 participants. The results showed that the combined regimen arm had no significant improvement of PFS (log hazard ratio = -0.228, 95% CI: -0.543 to 0.087, P = 0.157), ORR (odds ratio = 1.147 [95% CI: 0.577, 2.281], P = 0.695), DCR (odds ratio = 1.578 [95% CI: 0.428, 5.821], P = 0.493), and AEs, including fatigue and diarrhea (odds ratio = 0.833 [95% CI: 0.297, 2.333], P = 0.728 for fatigue and odds ratio = 2.268 [95% CI: 0.544, 9.448], P = 0.261 for diarrhea). Combination therapy may not provide a significant improvement in PFS, ORR, DCR, and incidence of AEs compared with monotherapy in patients with advanced NSCLC with EGFR mutations. Further research is needed to investigate the optimal sequencing of combination therapy in patients with NSCLC with different molecular targets to determine the most effective treatment strategy that can improve outcomes and quality of life for these patients.

Primary Tumor Resection for Stage IV Non-small-cell Lung Cancer Without Progression After First-Line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment: A Retrospective Case-Control Study.

In studies of stage IV epidermal growth factor receptor (EGFR)-mutant nonsmall-cell lung cancer (NSCLC), <10% of patients underwent surgery; thus, the effect of surgery in these patients remains unclear. We investigated whether primary lung tumor resection could improve the survival of patients with stage IV EGFR-mutant NSCLC without progression after first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. This retrospective case-control study included patients treated with first-line EGFR-TKIs without progression on follow-up imaging. Patients in the surgery group (n = 56) underwent primary tumor resection, followed by TKI maintenance therapy. Patients in the control group (n = 224; matched for age, metastatic status, and Eastern Cooperative Oncology Group performance status) received only TKI maintenance therapy. Local ablative therapy for distant metastasis was allowed in both groups. The primary endpoint was progression-free survival. The secondary endpoints were overall survival, failure patterns, and complications/adverse events. The median time from TKI treatment to surgery was 5.1 months. For the surgery and control groups, the median follow-up periods were 34.0 and 38.5 months, respectively, with a median (95% confidence interval) progression-free survival of 29.6 (18.9-40.3) and 13.0 (11.8-14.2) months, respectively (P < 0.001). Progression occurred in 29/56 (51.8%) and 207/224 (92.4%) patients, respectively. The median overall survival in the surgery group was not reached. The rate of surgical complications of grade ≥2 was 12.5%; complications were treated conservatively. Primary tumor resection is feasible for patients with EGFR-mutant nonprogressed NSCLC during first-line EGFR-TKI treatment and may improve survival better than maintenance EGFR-TKI therapy alone.

Efficacy and Prognosis of First-Line EGFR-Tyrosine Kinase Inhibitor Treatment in Older Adults Including Poor Performance Status Patients with EGFR-Mutated Non-Small-Cell Lung Cancer.

IntroductionEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutated non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR-TKIs in older patients including poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) is seldom investigated.MethodsWe enrolled patients 65 years or older with EGFR-mutated Stage IIIB–IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment. Clinical and demographic characteristics were reviewed and analyzed, including age, sex, PS, smoking history, EGFR mutation type, treatment regimen, progression-free survival (PFS), and overall survival (OS).ResultsFrom January 2015 to December 2019, a total of 237 patients were included, 205 of whom were eligible for efficacy and outcome analyses. Among them, 91 (44.4%) were categorized as poor PS (2–4). Compared with patients categorized as good PS (0–1), those with poor PS were older (79 versus 75 years), had a higher proportion of brain metastases (41.8% versus 25.4%), more comorbidities (74.7% versus 54.4%), and more likely to be treated with first-generation TKIs (74.7% versus 57.0%). The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, <3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS.ConclusionIn older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and <3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.

High fibrinogen-albumin ratio index predicts poor prognosis for lung adenocarcinoma patients undergoing epidermal growth factor receptor-tyrosine kinase inhibitor treatments.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) have become the preferred therapy as first-line treatment of non-small cell lung cancer patients harboring sensitizing EGFR mutations. However, the prognostic indicators are limited. The present study aimed to assess the prognostic value of immune-inflammation factors, fibrinogen-albumin ratio index (FARI), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) in EGFR-Mutant lung adenocarcinoma patients receiving first-generation EGFR-TKIs treatment.194 patients were included in this retrospective analysis. FARI was calculated as fibrinogen / albumin. Receiver operating characteristic curve was used to evaluate the optimal cut-off value for FARI, NLR, and PLR to progression free survival (PFS). Univariate and multivariate survival analysis were performed to identify factors correlated with PFS and overall survival (OS).Applying cut-offs of ≥0.08 (FARI), ≥3.28 (NLR), and ≥273.85 (PLR), higher FARI or NLR was associated with worse Eastern Cooperative Oncology Group performance status (ECOG PS) (P = .018, .002, respectively), and there were more males in high NLR group (P = .043). In univariate analysis, ECOG PS status, NLR, PLR, and FARI were significantly associated with PFS (P = .017, .004, <.001, .001, respectively) as well as OS (P < .001, = .001, .002, .023, respectively). In multivariate analysis, PLR (hazard ratios [HR] 1.692; 95% CI 1.054–2.715; P = .029) and FARI (HR 1.496; 95% CI 1.031–2.172; P = .034) were independent prognostic factors for PFS. While only ECOG PS status (HR 2.052; 95% CI 1.272–3.310; P = .003) was independently correlated with OS.FARI is independently associated with PFS in EGFR-Mutant lung adenocarcinoma patients receiving first-line EGFR-TKIs treatment.

Association between EGFR exon 19 or exon 21 mutations and survival rates after first-line EGFR-TKI treatment in patients with non-small cell lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) who have an EGFR mutation. However, little has been reported about the association between EGFR exon 19 deletions or an exon 21 mutation (specifically the L858R point mutation) and survival rates following first-line EGFR-TKI treatment in patients with NSCLC. As a retrospective study, 72 patients with stage IIIB/IV NSCLC carrying EGFR mutations (exon 19 deletions or an exon 21 mutation) were enrolled between 1 January 2008 and 31 December 2013, and all of the patients received first-line EGFR-TKI treatment. The associations between EGFR mutation status or clinical characteristics and response rate (ORR), progression-free survival (PFS) or overall survival (OS) were analyzed. Patients with exon 19 deletions (37 cases) had a higher ORR (75.7 vs. 51.4%; P=0.032), disease control rate (DCR; 89.2 vs. 68.6%; P=0.031), modified median PFS (13.2 vs. 10.8 months; P=0.030) and OS (30.2 vs. 25.6 months; P=0.030) compared with those with an exon 21 mutation (35 cases). Cox multivariate analysis indicated that sex, histological type and smoking history were key factors that affected PFS and OS. Mutations status was associated with PFS, but not OS. Following EGFR-TKI therapy, a better ORR, DCR, PFS and OS was observed in patients with EGFR deletions in exon 19 compared with those with an exon 21 mutation. The EGFR mutation status of patients with non-small cell lung cancer may therefore predict the efficacy and prognosis of EGFR-TKI.

The relationship between preliminary efficacy and prognosis after first-line EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment of advanced non-small cell lung cancer.

Nowadays, patients with EGFR tyrosine kinase inhibitor (EGFR-TKI)-sensitive advanced non-small cell lung cancer (NSCLC) receive EGFR-TKIs as first-line treatment. We aimed to analyze the relationship between preliminary efficacy (tumor shrinkage within 1 month) and progression-free survival (PFS) after first-line EGFR-TKI treatment. A total of 82 patients with EGFR-TKI-sensitive advanced NSCLC confirmed by histopathology from January 2013 to January 2017 were retrospectively analyzed. All patients received first-line EGFR-TKI treatment and follow-up at Shanghai Chest Hospital. Of a total of 82 patients, 42 (51.2%) patients achieved partial response (PR) within 1 month, and 40 (48.8%) patients achieved stable disease (SD: -30% to 0) within 1 month. The median PFS among all patients was 10 months. The median PFS in patients achieving PR within 1 month was 10.0 months. The median PFS in patients achieving SD (-30% to 0) within 1 month was 9.3 months. There was no statistically significant difference between PR within 1 month and SD (-30% to 0) within 1 month (P=0.620). In the EGFR-sensitive mutation subgroup, there was also no statistically significant difference between PR within 1 month and SD (-30% to 0) within 1 month. Univariate and multivariate analysis of first-line EGFR-TKI treatment showed that age, EGFR mutation type, and T staging had effects on PFS. Patients who were more than 65 years old, had EGFR 19del mutation, along with a T staging less than 4, had a longer PFS; these differences were statistically significant. Liver metastasis, bone metastasis, and brain metastasis were not shown to be related to PFS. For patients with EGFR-TKI-sensitive advanced NSCLC, there is no correlation between preliminary efficacy (tumor shrinkage within 1 month) and PFS after first-line EGFR-TKI treatment.

Impact on prognosis of rebiopsy in advanced non-small cell lung cancer patients after epidermal growth factor receptor-tyrosine kinase inhibitor treatment: a systematic review

BackgroundOsimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy reveals T790M mutation after the first-line EGFR-TKI treatment. However, the prognosis of patients after rebiopsy, the most important outcome for cancer patients, has not been described sufficiently. This systematic review aimed to clarify whether rebiopsy contributes to improved prognosis in the first- or second-generation EGFR-TKI refractory patients.MethodsUsing free word and control terms related to “non-small cell lung cancer” and “rebiopsy,” we searched studies from Medical Literature Analysis and Retrieval System Online via PubMed, Embase, Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform. We included cohort studies and case reports written in English and judged whether each study answers our research questions.ResultsOf the 144 studies included, only one reported the prognosis of patients with/without rebiopsy showing that in EGFR-TKI refractory non-small cell lung cancer patients, the post-progression survival (PPS) was significantly longer in patients who received rebiopsy and treatment based on a resistant mechanism (median PPS 24.2 months) than those who received rebiopsy and salvage regimen (median PPS 15.2 months, p = 0.002) and who did not receive rebiopsy (median PPS 9.7 months, p < 0.001). Most of the other studies reported the detection rate of T790M mutation or rebiopsy procedure.ConclusionsOnly a few previous studies have investigated the effectiveness of rebiopsy. Hence, further study is needed to determine the prognosis or adverse events of rebiopsy.

Factors associated with improvement in symptoms and quality of life for first-line EGFR-tyrosine kinase inhibitor treatment in patients with EGFR-mutated non-small-cell lung cancer - A multicenter prospective SMILE study

Introduction: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard first-line treatment for advanced EGFR-mutated NSCLC patients. Factors associated with symptoms and quality of life (QOL) improvements have not been investigated.Methods: We conducted a multicenter, prospective study to evaluate improvements in QOL and symptoms in NSCLC patients treated with first-line EGFR-TKIs. QOL was assessed using the instrument of Functional Assessment of Cancer Therapy-Lung questionnaire (FACT-L) and Treatment Outcome Index (TOI). Assessment of symptoms was evaluated using the Lung cancer subscale (LCS).Results: Eligible subjects included 280 patients for endpoint analyses. The mean FACT-L score increased by 4.0 ± 15.56 at Week 2 (p<0.001), 5.1 ± 18.48 at Week 4 (p<0.001), and 4.2 ± 20.27 at Week 12 (p=0.001). Similarly, a 2.3 ± 11.65 (p<0.001), 3.2 ± 13.59 (p<0.001), and 2.4 ± 14.34 (p=0.009) increase in mean TOI score were observed at Weeks 2, 4 and 12, respectively. For LCS, it was slightly increased by 1.7 ± 4.61, 2.0 ± 5.50, and 2.0 ± 5.36 at Weeks 2, 4, and 12 (all p<0.001), respectively. Subgroup analyses showed patients who were ex-smokers or with at least 3 metastatic sites were associated with symptoms improvement. Patients who were ex-smokers, with at least 3 metastatic sites, a PS of 1, or treated with gefitinib were associated with QOL improvement.Conclusions: In EGFR -mutated NSCLC patients who were treated with first-line EGFR-TKIs, these ex-smokers or with 3 or more metastatic sites were associated with improvements in symptoms and QOL.

Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR-TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded. Overall, 20 patients with a median age of 79.5years (range 75-85years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted. Second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first-line cytotoxic drug chemotherapy.

Clinical benefit from EGFR-TKI plus ginsenoside Rg3 in patients with advanced non-small cell lung cancer harboring EGFR active mutation.

PurposeAcquired resistance is a bottleneck that restricts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for lung cancer. Ginsenoside Rg3 is an antiangiogenic agent which can down-regulate the expressions of vascular endothelial growth factor (VEGF) and EGFR. Combination of EGFR-TKI and ginsenoside Rg3 may be a promising strategy to delay acquired resistance. This retrospective study explored the efficacy and safety of this combined regimen in patients with EGFR mutation and advanced non-small cell lung cancer (NSCLC).ResultsBy the deadline of March 31th 2016, the median follow-up period reached 22.9 months. The median PFS was significantly longer in group A than in group B (12.4 months vs 9.9 months, P = 0.017). In addition, ORR was significantly higher in group A than in group B (59.6% vs 41.7%, P = 0.049). The median OS in group A showed no extended tendency compared with that in group B (25.4 months vs 21.4 months, P = 0.258). No significant difference in side effects was found between the two groups.MethodsA total of 124 patients with advanced NSCLC and EGFR active mutation were collected and analyzed. All of them were treated with first-line EGFR-TKI and divided into two groups. In group A (n=52), patients were administered EGFR-TKI plus ginsenoside Rg3 at standard doses. In group B (n=72), patients received EGFR-TKI alone. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and side effects were analyzed.ConclusionsGinsenoside Rg3 improves median PFS and ORR of first-line EGFR-TKI treatment in EGFR-mutant advanced NSCLC patients, thus providing a new regimen to delay acquired resistance of EGFR-TKI.

Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21.

BackgroundEpidermal growth factor receptor (EGFR) mutations, including a known exon 19 deletion (19 del) and exon 21 L858R point mutation (L858R mutation), are strong predictors of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment in lung adenocarcinoma. However, whether patients carrying EGFR 19 del and L858R mutations exhibit different responsiveness to EGFR-TKIs and what are the potential mechanism for this difference remain controversial. This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.MethodsOf 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858R mutations, 532 received EGFR-TKI treatment and were included in this study. EGFR 19 del and L858R mutations were detected by using denaturing high-performance liquid chromatography (DHPLC). T790M mutation, which is a common resistant mutation on exon 20 of EGFR, was detected by amplification refractory mutation system (ARMS). Next-generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations.ResultsOf the 532 patients, 319 (60.0%) had EGFR 19 del, and 213 (40.0%) had L858R mutations. The patients with EGFR 19 del presented a significantly higher overall response rate (ORR) for EGFR-TKI treatment (55.2% vs. 43.7%, P = 0.017) and had a longer progression-free survival (PFS) after first-line EGFR-TKI treatment (14.4 vs. 11.4 months, P = 0.034) compared with those with L858R mutations. However, no statistically significant difference in overall survival (OS) was observed between the two groups of patients. T790M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment, and there was no significant difference in the co-existence of T790M mutation with EGFR 19 del and L858R mutations before EGFR-TKI treatment (5.6% vs. 8.8%, P = 0.554) or after treatment (24.4% vs. 35.4%, P = 0.176). In addition, 24 patients with EGFR 19 del and 19 with L858R mutations were analyzed by NGS, and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.ConclusionsPatients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858R mutations. Whether the heterogeneity of tumors with EGFR 19 del and L858R mutations contribute to a therapeutic response difference needs further investigation.

Effectiveness of EGFR-TKIs versus chemotherapy as first-line treatment for advanced non-small cell lung cancer: a meta-analysis

背景与目的表皮因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKI）应用于非小细胞肺癌（non-small cell lung cancer, NSCLC）一线治疗取得较好的临床疗效，然而EGFR-TKI一线用药选择仍面临很多问题。本研究应用循证医学的方法对NSCLC患者临床特征及基因突变情况对一线EGFR-TKIs治疗及化疗获益进行分析，以便指导临床用药。方法用计算机检索Pubmed、Embase、American Society of Clinical Oncology（ASCO）、European Society for Medical Oncology（ESCO）及生物医学数据库等数据库，寻找出EGFR-TKI与化疗相比一线治疗NSCLC的疗效的随机对照研究（randomized controlled trials, RCT）。对纳入RCT进行资料提取和质量评价，采用Review Manager 5.2软件分析、对比NSCLC患者在TKI治疗中的疗效。结果纳入的14项研究，共5, 000例患者。Meta分析结果显示，EGFR基因突变的NSCLC患者，EGFR-TKIs治疗与化疗相比有较好的近期有效率（RR=2.31; 95%CI: 1.88-2.84）和延长无疾病进展时间（progression free survival, PFS）（HR=0.39; 95%CI: 0.30-0.49），总生存时间（overall survival, OS）上两者无明显差异（HR=0.99; 95%CI: 0.84-1.16）。临床选择（亚裔、腺癌、不吸烟）NSCLC患者，EGFR-TKIs一线治疗与化疗相比也有较好的近期有效率（RR=1.30; 95%CI: 1.15-1.47），PFS和OS无差异（HR=0.93; 95%CI: 0.58-1.49）（HR=0.91; 95%CI: 0.81-1.02）。未经选择的患者，一线EGFR-TKIs治疗有效率、PFS与化疗无差异，但OS劣于一线接受化疗患者。结论EGFR突变的NSCLC患者一线EGFR-TKIs获益更多；对于不能耐受化疗的亚裔、腺癌、不吸烟患者，推荐一线EGFR-TKIs治疗；未经选择的NSCLC患者一线EGFR-TKIs治疗临床无获益，而且一线EGFR-TKI治疗的OS明显低于一线化疗。

Post-progression survival after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations.

e19005 Background: Non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) mutation show a survival benefit on treatment with EGFR-tyrosine kinase inhibitor (EGFR-TKI); however, few studies report on post-progression tumor behavior after treatment with EGFR-TKI. Methods: We retrospectively reviewed clinical data of stage IV or recurrent NSCLC patients harboring the EGFR mutation, who received EGFR-TKI as first-line treatment in our institute from 2009 to 2011. Results: Thirty-six patients received EGFR-TKI as first-line therapy. Thirty of these patients with recurrent NSCLC were enrolled in this study. The median age of the patients was76 years (range, 38–97), and the male/female ratio was 4/26. The median progression-free survival (PFS) after EGFR-TKI treatment was 8.2 months. Sites of relapse in patients with progressive disease (PD) were the brain, pleural effusion, bone, and lung (n=5, 13, 6, and 8, respectively). Twenty-one patients received sequential therapy: 11 patients received continued EGFR-TKI treatment beyond PD and 10 patients received second-line therapy. Second-line therapies were platinum-based doublet therapy, monotherapy, and another cycle of EGFR-TKI (n = 6, 2, and 2 patients, respectively). Post-progression survival (PPS) of all the patients after treatment with EGFR-TKI was 9.2 months, whereas that of patients who received EGFR-TKI as second-line chemotherapy was 14 months. Subgroup analysis according to the site of relapse showed that after first-line EGFR-TKI treatment, PFS tended to be higher for patients with a relapse in the brain (11.6 months) than for patients with sites of relapse other than the brain (8.2 months). Conclusions: PPS after EGFR-TKI therapy in patients treated with second-line chemotherapy was similar to the OS of NSCLC patients without an EGFR mutation. Subgroup analysis showed that patients with a relapse in the brain might survive longer.

Clinical observation of EGFR-TKI as a first-line therapy on advanced non-small cell lung cancer

背景与目的研究表明，一线表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKI）治疗晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的客观缓解率及无进展生存期明显优于铂二联的化疗，且耐受性更好。本研究旨在分析EGFR-TKI一线治疗晚期EGFR突变阳性的NSCLC患者的疗效与耐受性。方法54例晚期NSCLC患者肿瘤标本采用直接测序法证实EGFR活化突变（外显子19缺失或外显子21点突变），一线给予EGFR-TKI口服治疗直至疾病进展，观察疗效及不良反应，并进行生存随访。结果54例患者外显子19缺失33例（61%），外显子21点突变21例（39%）。均一线接受EGFR-TKI治疗，总体缓解率为90%，中位无进展生存期（progression free survival, PFS）为8.3个月，中位生存期为19.5个月；外显子19缺失患者的中位PFS（9.0个月）较21点突变（7.0个月）时间长（P=0.002）。外显子19缺失患者的中位总生存期（overall survival, OS）（25.0个月）较21点突变（16.0个月）时间长（P=0.001）；吉非替尼与厄洛替尼疗效相当，但吉非替尼组安全性更好；最常见的不良事件为皮疹和腹泻，有2例患者（4%）出现了3度皮肤毒性反应，2例患者（4%）出现了3度的转氨酶升高，1例患者（1%）出现了3度口腔炎。结论存在EGFR基因突变的晚期NSCLC患者一线接受EGFR-TKI治疗安全有效，且外显子19缺失比L858R突变疗效更优。