The role of EGFR inhibitors as adjuvant therapy for EGFR mutation positive non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8508-8508
Author(s):  
Peng Xie ◽  
Wenjie Tang ◽  
Xiaolin Li ◽  
Xindong Sun ◽  
Jinming Yu
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Egfr Tki ◽  
Egfr Tkis

8508 Background: Cisplatin-based chemotherapy as adjuvant therapy for resected NSCLC has reached its plateau, and was limited by high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as adjuvant therapy for targeted patients. Methods: Studies were identified via an electronic search on Pubmed, EMBASE, ISI Web of Science, ScienceDirect, SpringerLink, The Cochrane library and so on. Pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis. Registration number: PROSPERO (CRD42018093144). Results: There were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta-analysis. Results showed that adjuvant treatment with EGFR-TKIs can prolong both OS and DFS when compared to treatment without TKIs as adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I2= 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P < 0.00001; heterogeneity I2= 37%, P = 0.1). Results of predefined subgroup analyses in this meta-analysis suggested a greater DFS with EGFR-TKI mono compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p = 0.3). And we also find that treatment with EGFR-TKI plus chemotherapy was associated with significantly longer DFS as well as OS than chemotherapy mono in patients with completely resected EGFR-mutant NSCLC (DFS: OR, 0.48; 95%CI, 0.34-0.68; P < 0.00001; heterogeneity I2= 15%, P = 0.29; OS: OR, 0.50; 95% CI, 0.31-0.78; P = 0.003; heterogeneity I2 = 57%, P = 0.05). And less grade 3 or higher AEs were observed in the TKIs group (OR, 0.22; 95% CI, 0.14 to 0.37, P < 0.00001; heterogeneity I2= 22%, P = 0.28). Conclusions: Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completed resected patients with EGFR mutation-positive NSCLC. This project was supported by the National Natural Science Foundation of China (Grant No. 81502667), Key Research and Development Plan of Shandong, China (Grant No. 2016GSF201167).

scholarly journals A phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected non-small-cell lung cancer with EGFR mutation (West Japan Oncology Group 11719L/ADJUST study)

2021 ◽  
Vol 13 ◽  
pp. 175883592098764
Author(s):  
Ryota Shibaki ◽  
Hiroaki Akamatsu ◽  
Terufumi Kato ◽  
Kazumi Nishino ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Egfr Mutation ◽  
Phase Ii Study ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Egfr Mutated ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is a standard treatment in EGFR-mutated advanced non-small-cell lung cancer (NSCLC); however, previous data have suggested that EGFR-TKI has limited potential as adjuvant therapy. On the contrary, based on subset analysis with the immune checkpoint inhibitor (ICI) plus platinum-doublet chemotherapy in advanced NSCLC with EGFR mutation, we hypothesized that this combination was worth testing as adjuvant therapy in patients with EGFR-mutated NSCLC. Methods: Herein, we introduce our phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected NSCLC with EGFR mutation. Accrued patients will be pathological stage II–IIIA with completely resected NSCLC and whose tumors have EGFR mutation. Treatment comprises four cycles of cisplatin plus vinorelbine combined with atezolizumab followed by maintenance with atezolizumab. The primary endpoint is the disease-free survival (DFS) rate at 2 years. Secondary endpoints are DFS, overall survival, and safety. In total, 18 patients will be enrolled in this study. Discussion: Ongoing phase III trials of adjuvant ICI allow the inclusion of patients with EGFR mutation, but our current trial will provide the earliest clinical data on the efficacy of platinum-doublet chemotherapy with atezolizumab.

A practical decision-making strategy based on clinical triple features for EGFR-TKIs to treat advanced non-small cell lung cancer patients with unknown EGFR mutation status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19082-e19082
Author(s):  
Di Zheng ◽  
Jiying Wang ◽  
Bing Lu
Keyword(s):  
Lung Cancer ◽  
Salvage Therapy ◽  
Egfr Mutation ◽  
Response Rate ◽  
Small Cell ◽  
Smoking History ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Egfr Tki ◽  
Egfr Tkis

e19082 Background: EGFR mutated lung cancers are strongly associated with clinical characteristics of never- smoking history and adenocarcinoma histology type, and tended to develop multiple pulmonary metastases.Whether multiple pulmonary metastatic lung adenocarcinomas with never-smoking history would respond to EGFR-TKIs as those harboring EGFR active mutation remains unclear. Methods: 223 consecutive metastatic non-small cell lung cancer (NSCLC) patients with unknown EGFR status who received EGFR-TKIs as salvage therapy after failure of previous platinum-based chemotherapy in Shanghai Pulmonary hospital between 2009 and 2011 were included to the study. Available CT scans, routinely performed at baseline and one month after the start of EGFR-TKIs therapy, were reviewed independently by two investigators. For the purposes of this study, diffuse pulmonary metastatic nodules were defined as multiple nodules distributed diffusely throughout the whole lung with at least 20 nodules within the unilateral lung field. Paraffin embedded tissues were available for 45 of 223 patients for EGFR gene mutation test. Results: Of 134 never-smokers with lung adenocarcinoma,70 patients responded to EGFR-TKIs with an objective response rate (ORR) of 52.2% (70/134), and the ORR for the 62 patients with diffuse pulmonary metastatic nodules was 79% (49/62). Among the 20 patients with confirmed EGFR mutation (based on the available 45 archived specimen), the ORR was 75% (15/20). The multivariate analyses showed that the presence of diffused multiple pulmonary metastatic nodules, activating EGFR mutation and female are independent predictive factors of the response to EGFR-TKIs. Conclusions: Patient selection based on specific clinical features to recieve EGFR-TKI treatment yield high response rate comparable to that selected by EGFR mutation status. It is practical to consider EGFR-TKI as salvage therapy in non-smoking patients with lung adenocarcinoma characterized by diffuse pulmonary nodules when EGFR mutation testing is a challenge.

scholarly journals Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jie-Tao Ma ◽  
Yi-Jia Guo ◽  
Jun Song ◽  
Li Sun ◽  
Shu-Ling Zhang ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Formula Group ◽  
Exon 19 Deletion ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Egfr Tkis

Purpose. A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors ( A + T ) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Methods. PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). Results. Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone ( HR = 0.60 ; P < 0.01 ) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups ( HR = 0.933 ; P = 0.551 ) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups ( RR = 0.774 ; P = 0.008 ). There was no difference in the positive rates of acquired T790M mutation between the two groups ( RR = 0.967 ; P = 0.846 ). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group ( RR = 0.881 ; P = 0.002 ). Conclusion. Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.

Optimal Adjuvant Therapy in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer Harboring EGFR Mutations

2020 ◽  
Vol 43 (12) ◽  
pp. 686-693
Author(s):  
Miaomiao Wen ◽  
Lei Wang ◽  
Xuejiao Wang ◽  
Sanhu Yang ◽  
Ying Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Stage Iiia ◽  
Egfr Tki ◽  
Egfr Tkis

<b><i>Background:</i></b> Some non-small-cell lung cancer (NSCLC) patients are unexpectedly diagnosed with stage IIIA-N2 disease at the time of thoracoscopy or thoracotomy. Because of the limited statistical evidence of induction chemotherapy for these patients, it is necessary to develop more profound treatment strategies. <b><i>Methods:</i></b> The demographic and clinical characteristics of patients with stage IIIA-N2 NSCLC harboring epidermal growth factor receptor (EGFR) mutations after radical resection were retrospectively reviewed. The patients were divided into 3 groups based on treatment: EGFR tyrosine kinase inhibitors (EGFR-TKIs, erlotinib or gefitinib), adjuvant chemotherapy (docetaxel plus cisplatin), and combination treatment (chemotherapy plus EGFR-TKIs). The effect of adjuvant therapy on survival rate was assessed using univariate and Cox regression analyses. <b><i>Results:</i></b> Patients receiving EGFR-TKIs alone showed significantly improved disease-free survival (DFS; <i>p</i> = 0.025) when compared to those receiving chemotherapy alone. Compared to chemotherapy alone, the combination of chemotherapy and EGFR-TKIs resulted did not significantly improve DFS (<i>p</i> &#x3c; 0.001) and overall survival (OS <i>p</i> &#x3c; 0.001). The combination of EGFR-TKIs with chemotherapy as adjuvant therapy led to improvements in both DFS (<i>p</i> = 0.116) and OS (<i>p</i> = 0.039) compared to patients receiving a EGFR-TKI monotherapy. Toxicities were mild in the 3 treatment groups. <b><i>Conclusions:</i></b> Our study demonstrated that adjuvant EGFR-TKI treatment significantly increased the DFS of patients with stage IIIA-N2 NSCLC when compared with cisplatin-based chemotherapy. The use of EGFR-TKIs and chemotherapy is recommended in the setting of combined-modality therapy.

Role of Adjuvant Chemotherapy in Patients With Resected Non–Small-Cell Lung Cancer: Reappraisal With a Meta-Analysis of Randomized Controlled Trials

2004 ◽  
Vol 22 (19) ◽  
pp. 3860-3867 ◽  
Author(s):  
Katsuyuki Hotta ◽  
Keitaro Matsuo ◽  
Hiroshi Ueoka ◽  
Katsuyuki Kiura ◽  
Masahiro Tabata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Literature Search ◽  
Meta Analysis ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc

Purpose The role of adjuvant chemotherapy in patients with resected non–small-cell lung cancer (NSCLC) remains to be defined. This study was aimed at re-evaluating the effectiveness of adjuvant chemotherapy in patients with resected NSCLC, by performing a meta-analysis of relevant trials. Methods We performed a literature search to identify trials reported after the publication of a meta-analysis in 1995, comparing patients with NSCLC receiving chemotherapy after surgery with those undergoing surgery alone. The hazard ratio (HR) was estimated to assess the survival advantage of adjuvant chemotherapy. Results Eleven trials conducted on a total of 5,716 patients were identified by the literature search. In these trials, hazard ratio estimates suggested that adjuvant chemotherapy yielded a survival advantage over surgery alone (HR, 0.872; 95% CI, 0.805 to 0.944; P = .001). In a subset analysis, both cisplatin-based chemotherapy (HR, 0.891; 95% CI, 0.815 to 0.975; P = .012) and single-agent therapy with tegafur and uracil (UFT; HR, 0.799; 95% CI, 0.668 to 0.957; P = .015) were found to yield a significant survival benefit. The toxicities of adjuvant chemotherapy were found to be generally mild. Conclusion This is the first updated meta-analysis demonstrating the importance of cisplatin-based chemotherapy and single-agent UFT therapy as adjuvant chemotherapy in the treatment of resected NSCLC. Although the results must be carefully interpreted because of one limitation (the meta-analysis was performed with abstracted data), they raise critical issues that must be resolved in future studies.

scholarly journals Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: Are They Different from Those with Common EGFR Mutations?

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 326
Author(s):  
Hyun Ae Jung ◽  
Sehhoon Park ◽  
Jong-Mu Sun ◽  
Se-Hoon Lee ◽  
Jin Seok Ahn ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Response Rate ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Compound Mutation ◽  
Egfr Tki ◽  
Egfr Tkis

Approximately 10% of the epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are uncommon EGFR mutations. Although the efficacy of second (2G) or third generation (3G) EGFR tyrosine kinase inhibitors (EGFR-TKIs) in the patients with uncommon EGFR mutation has been proven, further studies are warranted to define the optimal treatment approach for uncommon EGFR mutation-positive NSCLC. This study retrospectively investigated the treatment patterns and outcomes of patients with uncommon EGFR mutation-positive NSCLC from January 2011 to December 2019 at the Samsung Medical Center, Seoul, Korea. During the study, 2121 patients with EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. Of this, 135 (6.4%) patients harbored uncommon EGFR mutations. Of 135, 54 (40%, 54/135) patients had overlapping mutations with major EGFR mutations. The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8–13.5), 11.7 months (95% CI: 6.6–16.7), 7.7 months (95% CI: 4.9–17.4), and 5.0 months (95% CI: 3.7–6.1) for major uncommon EGFR mutation (G719X, L861Q), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The median overall survivals (OSs) were 25.6 months (16.9–34.2), 28.8 (95% CI: 24.4–33.4), 13.5 months (95% CI: 7.4–27.8), and 9.4 months (95% CI: 3.4–10.5) for major uncommon EGFR mutation (G719X), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The response rate, median PFS, and OS were 63.3%, 16.3 months (95% CI: 15.6–16.9), and 37.5 months (95% CI: 35.4–39.6) for common EGFR mutation-positive NSCLC. After failing 1L EGFR-TKI, repeated tissue or liquid biopsy were carried out on 44.9% (35/78) of patients with T790M detected in 10/35 (28.6%) patients. With subsequent 3G EGFR-TKI after failing the first-line EGFR-TKI, the ORR and PFS for 3G EGFR-TKI were 80% and 8.9 months (95% CI: 8.0–9.8). These patients showed a median OS of 34.6 months (95% CI: 29.8–39.4). The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common EGFR mutations. T790M was detected in 28.6% of the uncommon EGFR mutation-positive patients for whom prior 1G/2G EGFR-TKIs failed and underwent repeat biopsy at the time of progression.

scholarly journals Network meta analysis of first-line therapy for advanced EGFR mutation positive non-small-cell lung cancer: updated overall survival

2020 ◽  
Vol 16 (36) ◽  
pp. 3107-3116
Author(s):  
MeganS Farris ◽  
Kelly A Larkin-Kaiser ◽  
Tayler Scory ◽  
Devon Boyne ◽  
Keith D Wilner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Egfr Tkis

Aim: To update overall survival (OS) results from a previous network meta analysis comparing the relative clinical efficacy of epidermal growth factor receptor-targeted tyrosine kinase inhibitors ( EGFR TKIs) for EGFR mutation positive ( EGFR+) advanced non-small-cell lung cancer (NSCLC). Materials & methods: A Bayesian network meta analysis was conducted using updated/mature randomized controlled trial OS results in response to first-line EGFR TKI therapies. Results: Dacomitinib showed a numerical improvement of OS relative to other EGFR TKIs: afatinib (hazard ratio [HR]: 0.87; 95% credible interval [CrI]: 0.61–1.24), erlotinib (HR: 0.79; 95% CrI: 0.44–1.42), gefitinib (HR: 0.75; 95% CrI: 0.59–0.95) and osimertinib (HR: 0.94; 95% CrI: 0.68–1.29). Conclusion: Dacomitinib should be considered as a first-line treatment option for patients diagnosed with advanced EGFR+ NSCLC.

scholarly journals First- and Second-Generation EGFR-TKIs Are All Replaced to Osimertinib in Chemo-Naive EGFR Mutation-Positive Non-Small Cell Lung Cancer?

2019 ◽  
Vol 20 (1) ◽  
pp. 146 ◽  
Author(s):  
Masayuki Takeda ◽  
Kazuhiko Nakagawa
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Second Generation ◽  
Egfr Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
First And Second Generation ◽  
Egfr Tki ◽  
Egfr Tkis

Activating mutations of the epidermal growth factor receptor gene (EGFR) are a driving force for some lung adenocarcinomas. Several randomized phase III studies have revealed that treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) results in an improved progression-free survival (PFS) compared to standard chemotherapy in chemonaive patients with advanced non–small cell lung cancer (NSCLC), selected based on the presence of EGFR mutations. Patients treated with second-generation EGFR-TKIs have also shown an improved PFS relative to those treated with first-generation EGRF-TKIs. Osimertinib is a third-generation EGFR-TKI that still irreversibly inhibits the activity of EGFR after it has acquired the secondary T790M mutation that confers resistance to first- and second-generation drugs. Its efficacy has been validated for patients whose tumors have developed T790M-mediated resistance, as well as for first-line treatment of those patients with EGFR mutation–positive NSCLC. Although there are five EGFR-TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) currently available for the treatment of EGFR-mutated lung cancer, the optimal sequence for administration of these drugs remains to be determined. In this review, we addressed this issue with regard to maximizing the duration of the EGFR-TKI treatment.

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