Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung CANCER (original) (raw)
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Clinical Cancer Research, 2009
Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene are associated with an increased response to gefitinib in patients with non^small cell lung cancer. We have examined the impact of gefitinib on progression-free survival and overall survival in patients with EGFR mutation^positive non^small cell lung cancer. Experimental Design: We searched for all clinical trials that prospectively evaluated the efficacy of gefitinib for advanced non^small cell lung cancer with EGFR mutations in Japan. We did a combined analysis based on individual patient data from the identified trials. Results: Seven eligible trials were identified for a total of 148 non^small cell lung cancer patients with EGFR mutations. The overall response rate to gefitinib was 76.4% [95% confidence interval (95% CI), 69.5-83.2]. The median progression-free survival and overall survival were 9.7 months (95% CI, 8.2-11.1) and 24.3 months (95% CI, 19.8-28.2), respectively. Good performance status and chemotherapy-naI« ve status were significantly associated with a longer progression-free survival or overall survival. Of the 148 patients, 87 received gefitinib as a first-line therapy, whereas 61received systemic chemotherapy before gefitinib treatment. The median progression-free survival after the start of first-line therapy was significantly longer in the gefitinib-first group than in the chemotherapy-first group (10.7 versus 6.0 months; P < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (27.7 versus 25.7 months; P = 0.782). Conclusions: Gefitinib monotherapy confers substantial clinical benefit in terms of progressionfree survival and overall survival in non^small cell lung cancer patients with EGFR mutations. Randomized trials comparing chemotherapy with gefitinib as a first-line treatment are warranted in such patients.
Oncotarget, 2016
Second-line treatment for advanced non-small-cell lung cancer (NSCLC) patients includes monotherapy with a third-generation cytotoxic drug (CT) or a tyrosine kinase inhibitor (TKI). These options are the actual standard for EGFR wild-type (WT) status, as patients with EGFR mutations achieve greater benefit by the use of TKI in first-line treatment. Some clinical trials and meta-analyses investigated the comparison between CT and TKI in second-line, but data are conflicting. We designed a retrospective trial to gather information about TKI sensitivity in comparison with CT. We selected from clinical records patients treated with at least 1 line of CT and at least 1 line of TKI. We collected data about age, sex, performance status, comorbidity, smoking status, histotype, metastatic sites, EGFR status, treatment schedule, better response and time-to-progression (TTP) for each line of treatment and overall survival (OS). 93 patients met selection criteria. Mean age 66,7 (range: 46-84). ...
Journal of the National Cancer Institute, 2017
We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC). Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided. Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P = .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0....
Nusantara Medical Science Journal, 2022
Introduction. Lung cancer is the type of non-small cell carcinoma (NSCLC) consists of non-squamous and squamous. Non-small cell lung cancer of non squamous types consist of adenocarcinoma and large cell carcinoma. Currently, lung cancer therapy is highly developed of chemotherapeutic agents to targeted therapy especially EGFR-TKI. This study aims to assess the survival rate of NSCLC patients who receive first line chemotherapy and those who recieve EGFR-TKI therapy at Wahidin Sudirohusodo hospital. Methods. This study is a retrospective study between 2017 to 2019 from the medical records of NSCLC patients who receive first-line chemotherapy and thise who recieve EGFR-TKI. Patients with platinum-based chemotherapy and EGFR-TKI with gefitinib therapy 1x250 mg/day or erlotinib 1x150mg/day and or afatinib 1x40 mg/day. Survival rate assessed from start to erect the diagnosis until the patient dies or when the study is discontinued. Result. From 239 subject of NSCLC patients consiste...
Oncology Letters, 2017
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.
Anticancer Research, 2019
Aim: To assess the patterns of disease progression in advanced/metastatic epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) on first-line treatment with erlotinib and identify potential prognostic factors for progression-free survival (PFS). Patients and Methods: Patients with stage IIIB/IV EGFR-mutation-positive NSCLC receiving first-line erlotinib were followed-up until 24 months after the last patient was enrolled or until premature withdrawal for any cause. Results: A total of 127 evaluable patients were enrolled. The median PFS and overall survival were 8.8 and 19.1 months, respectively. Disease progression was asymptomatic in 57.6% of patients and 53.3% developed new sites of metastasis. The presence of liver metastasis was identified as an independent prognostic factor for poor PFS. Conclusion: Metastatic progression with asymptomatic disease seems to be the predominant pattern of disease progression on first-line erlotinib in real-life practice in patients with advanced/metastatic EGFR-mutant NSCLC. Additionally, the presence of liver metastases may negatively affect PFS in these patients. Non-small-cell lung cancer (NSCLC), accounting for more than 85% of lung cancer cases, is the leading cause of cancer-related death worldwide (1). Most patients with NSCLC present with locally advanced or metastatic disease at initial diagnosis (1). The standard first-line treatment has traditionally consisted of platinum-based combination chemotherapy, but unfortunately, it provides a modest overall survival (OS) benefit (2-4). Increased knowledge of the molecular biology of lung cancer has shifted the treatment paradigm towards individualized therapy based on molecular characterization of the tumor. Accordingly, epidermal growth factor receptor (EGFR) has become an important molecular target in NSCLC, and has led to the development of tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, afatinib, and the third-generation TKI osimertinib. The presence of EGFRactivating mutations has been associated with a superior clinical benefit of EGFR-TKIs in patients with advanced NSCLC (5-8). Compared to standard first-line platinumbased chemotherapy, treatment with EGFR-TKIs has shown a significantly improved clinical outcome in patients harboring activating mutations in exons 18-21 which encode the tyrosine-kinase domain of the EGFR gene (5-10). EGFR-TKI therapy has, therefore, emerged as the standard of care in the first-line setting for patients with NSCLC and EGFRactivating mutations.
Open Access Macedonian Journal of Medical Sciences
Background: EGFR mutation is a genetic disorder that is often observed and examined in Non-Small Cell Lung Carcinoma. EGFR mutation detection aims to predict sensitivity to EGFR-TKI and acts as first-line therapy. Targeted therapy with EGFR-TKI can increase the survival rate of patients with Non-Small Cell Lung Cancer compared to chemotherapy. This study aims to obtain data on the survival rate of patients with Non-Small Cell Lung Carcinoma who received targeted therapy at H. Adam Malik Hospital. Methods: This study is a descriptive study with a retrospective cohort design carried out at the Oncology Polyclinic at RSUP H Adam Malik Medan for 5 years, from January 2014 to December 2018. The subjects of this study were all patients with lung cancer type adenocarcinoma who had received therapy with generation 1 or 2 EGFR TKI. Results: 99 patients were included as subjects of this study. From the study, the most influential factors on lung cancer were gender, age, and smoking addictio...