EGFR-TKIs plus chemotherapy demonstrated superior efficacy than EGFR-TKIs alone as first-line setting in advanced NSCLC patients with EGFR mutation and BIM deletion polymorphism

Lung Cancer ◽  
2018 ◽  
Vol 120 ◽  
pp. 82-87 ◽  
Author(s):  
Sangtian Liu ◽  
Yayi He ◽  
Tao Jiang ◽  
Shengxiang Ren ◽  
Fei Zhou ◽  
...  
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21099-e21099
Author(s):  
Huijuan Wang ◽  
Mengmeng Li ◽  
Mina Zhang ◽  
Zhang guo Wei ◽  
Xiangtao Yan ◽  
...  

e21099 Background: Liver metastasis is one of the most reasons for the poor prognosis of patients with advanced lung cancer. Seeking for active and effective treatment measures is very important for these patients. At present, the first-line standard treatment of the advanced NSCLC with EGFR mutation is EGFR-TKIs monotherapy. However, its efficacy is poor in the advanced non-small cell lung cancer with EGFR mutation and liver metastases. The objective of this study is to evaluate the efficacy of EGFR-TKIs plus chemotherapy in patients with EGFR mutation of advanced non-small cell lung cancer with liver metastases. Methods: The clinical data of a total of 384 advanced NSCLC patients with EGFR mutation positive who were admitted to The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital from February 2017 to June 2020 were retrospectively analyzed. There were 75 patients with liver metastases. Patients were divided into two groups, and accepted EGFR-TKIs monotherapy or EGFR-TKIs plus chemotherapy, respectively. All patients treatment response were evaluated by the RECIST1.1 Response evaluation criteria in solid tumors.Progression free-survival (PFS) were also analyzed. Results: In the study, 75 patients were finally screened. There were 37 patients in the EGFR-TKIs monotherapy group and 38 patients in the TKI plus chemotherapy group. The median follow-up time was 23.0 months. At the latest follow-up date (2021-01-01), 57 patients had disease progression and 35 patients had died. Comparing with EGFR-TKIs monotherapy,the first-line PFS of EGFR-TKI plus chemotherapy group was longer, and the median PFS was 12.7 months VS 7.4 months (P = 0.018).The ORR of primary lung lesions was no significant difference between these two groups(65.8%VS 51.4% P = 0.204), and DCR (97.4% VS 94.6% P = 0.981) also had no difference between two groups(P > 0.05). ORR of liver metastases in the EGFR-TKIs plus chemotherapy group was significantly higher than EGFR-TKIs monotherapy group ORR (65.8%VS 40.5%,P = 0.028). Conclusions: In advanced NSCLC patients with EGFR mutation and liver metastases, comparing with EGFR-TKIs monotherapy, taking EGFR-TKIs plus chemotherapy as first-line treatment had longer PFS, and better efficacy on liver lesions.


2018 ◽  
Vol Volume 12 ◽  
pp. 183-190 ◽  
Author(s):  
Miaomiao Wen ◽  
Jinghua Xia ◽  
Ying Sun ◽  
Xuejiao Wang ◽  
Xianghui Fu ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8042-8042 ◽  
Author(s):  
Jinji Yang ◽  
Ying Cheng ◽  
Mingfang Zhao ◽  
Qing Zhou ◽  
Hong hong Yan ◽  
...  

8042 Background: Pemetrexed or gefitinib is one of the standard second-line treatments for advanced non-squamousNSCLC in East Asia. The CTONG 0806 a multi-center, randomized, controlled, open-label phase II trial was designed to explore the efficacy of pemetrexed versus gefitinib as the second-line treatment in advanced NSCLC patients without EGFR mutation. Methods: The patients with locally advanced or metastatic, non-squamous NSCLC previously treated with platinum-based chemotherapy and no EGFR mutation in exons 18-21 were enrolled. Patients were 1:1 randomized to receive either gefitinib 250 mg per oral every day (G arm) or pemetrexed 500 mg/m2 iv day 1 with vitamin B12 and folic acid supplement every 21 days (P arm) until disease progression, unacceptable toxicity, or discontinuation of treatment due to other reason. The primary endpoint was progression-free survival (PFS). The secondary endpoints were 4-month and 6-month progression-free survival rate, overall survival (OS), objective response rate (ORR), quality of life using the FACT-L questionnaire and safety, EGFR and K-ras mutation status were evaluated and correlated with outcomes. Results: From Feb. 2009 to Aug. 2012, 157 evaluable patients were randomized (81 cases in G arm and 76 in P arm). Baseline age, gender, and ECOG performance status were balanced between arms. The primary endpoint of PFS was met with 1.6 months for G arm versus 4.8 months for P arm, the HR is 0.51 (95% CI 0.36~0.73, P<0.001). Overall response rates were 14.7 % and 13.3 % (P=0.814) and DCR were 32.0% and 61.3% (P<0.001) for G arm and P arm, respectively. OS data were not yet mature. More skin rash and diarrhoea were seen in G arm, but more fatigue and ALT increased in P arm. CTCAE grade 3 or 4 of AEs was 12.3% in G arm and 32.9% in P arm (p=0.002). The further analyses of efficacy evaluated by IRR and biomarkers analysis will be presented on the ground. Conclusions: CTONG0806 is the first trial to show significant improvements in PFS and DCR with pemetrexed compared with gefitinib in second-line setting for advanced NSCLC with EGFR wild type. Patients with EGFR wild type did not benefit from EGFR TKI gefitinb in second-line setting. Clinical trial information: NCT00891579.


2019 ◽  
Author(s):  
Wen Ouyang ◽  
Jing Yu ◽  
Yan Zhou ◽  
Jing Hu ◽  
Zhao Huang ◽  
...  

Abstract Purpose NSCLC patients with EGFR mutation was associated with higher incidence of developing brain metastasis (BM). BM is associated with high mortality. Reducing risk of BM becomes increasingly significant for achieving prolonged survival. The aim of the study was to explore the possible risk factors of developing BM during EGFR-TKIs treatment, and to identify the potential candidates for prophylactic cranial irradiation (PCI) or the first-line osimertinib treatment.Methods A total of 157 consecutive EGFR-mutated advanced NSCLC patients without BM at initial diagnosis in our institute between 2014 and 2018 were included. Comparisons of OS were performed based on BM status. The cumulative incidence of secondary BM was calculated by the Kaplan-Meier method, and the independent risk factors of secondary BM were investigated by multivariate analysis.Results Patients with secondary BM had worse survival (mOS: 28.6 months) than patients not-developing BM (mOS: 44.8 months). Moreover, the multivariate analysis indicated that age ≤ 49 years (P=0.035), number of extracranial metastases (P=0.013), and malignant pleural effusion (P =0.002) were independent risk factors of secondary BM. Furthermore, the 1-year actuarial risk of developing secondary BM in patients with no risk factor (n =101), 1 risk factor (n =46), and 2 risk factors (n =10) were 7.01%, 14.61%, and 43.75%, respectively (P<0.001).Conclusions Patients developing secondary BM during EGFR-TKIs treatment have worse outcomes. Our results suggested that EGFR-mutated advanced NSCLC patients with ≥ 1 risk factors were candidates for PCI or the first-line osimertinib treatment.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8078-8078 ◽  
Author(s):  
Tatsuya Yoshida ◽  
Kiyotaka Yoh ◽  
Koichi Goto ◽  
Shingo Matsumoto ◽  
Shigeki Umemura ◽  
...  

8078 Background: The progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation are clinically heterogeneous. The aim of this study is to evaluate progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation. Methods: From 2008 to 2012, 160 consecutive patients with advanced NSCLC harboring EGFR mutation were treated with EGFR-TKIs (erlotinib or gefitinib) at our institution. Among these patients, 104 patients who experienced RECIST PD assessed by radiologic findings were retrospectively evaluated for initial response on EGFR-TKIs, progression sites, focus of progression (solitary lesion or multiple lesions), patients status at RECIST PD, and post progression survival (PPS) from RECIST PD. Results: In 104 patients, 96 (92%) patients had EGFR major mutation (Exon 19 deletion and L858R), and 49 (47%) received EGFR-TKIs as first-line. The overall response rate and median progression free survival on EGFR-TKIs was 69 % and 8.2 months. At the time of RECIST PD, 44 (42%) patients had symptomatic, and 60 (58%) had asymptomatic. The progression sites were isolated CNS in 17 (16%) patients, isolated bone in 7 (7%), isolated pulmonary in 13 (12%), systemic in 67 (65%) patients. In the focus of progression, 24 (23%) patients have solitary lesion, and 80 (77%) have multiple lesions. After RECIST PD, 40 (38%) patients continued EGFR-TKIs, 25 (24%) were switched to cytotoxic agents, and 39 (38%) had best supportive care. 10 (10%) patients received local radiotherapy for isolated progression site (brain 6; bone 3; lung 1) and 8 of these patients continued EGFR-TKIs. The median PPS from RECIST PD was 10.6 months. Multivariate analysis identified that asymptomatic or solitary progression lesion at RECIST PD were associated with significantly longer PPS (asymptomatic: HR 0.34, 95% CI 0.19-0.58, P<0.001; solitary progression lesion: HR 0.39, 95% CI 0.16-83, P=0.013). Conclusions: The progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation have widely diversity. Further investigation for association between progression patterns at RECIST PD and clinical outcome after RECIST PD is warranted.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20524-e20524
Author(s):  
Francesca Zanelli ◽  
Maria Pagano ◽  
Candida Bonelli ◽  
Bruno Casali ◽  
Alberto Cavazza ◽  
...  

e20524 Background: over the past decade, personalized management based on the molecular features of tumours in patients with advanced non small-cell lung cancer (NSCLC) has entered routine clinical practice. The poor performance of many advanced NSCLC patients may limit invasive biopsies. The liquid biopsy is a diagnostic procedure performed on cancer-derived material obtained in blood samples. In this abstract, we will describe our experience with liquid biopsies. Methods: In the Reggio Emilia Clinical Cancer Centrefrom March 2016 to December 2016, 42 patients with advanced NSCLC were analyzed that had had or had already started first line therapy. The liquid biopsy was repeated at each imaging response evaluation by thoracic-abdominal compound tomography (CT) scan performed every 3 months. In the liquid biopsy, the mutational status of EGFR was analyzed with real time PCR (KIT cobas EGFR mutation test v2 CE-IVD Roche); in tissue, it was evaluated by pyrosequencing. Results: 21/42 liquid biopsies were EGFR-mutated (12/21 eson 19 and 9/21 eson 21). In 3/21 (14.3%) cases, the tissue biopsies showed wild type (WT) EGFR. 6 liquid biopsies were also performed at time 0 (diagnosis). All liquid biopsies of EGFR WT remained WT during treatment and imaging evaluation. The median number of liquid biopsy tests for patients was 2 (range 1-3). In 4/21 cases, T790M was performed: 3 cases in both liquid biopsies and tissue, and 1 case in tissue but not in liquid biopsy. TKi therapy was ineffective in this patient with T790M mutation detected in tissue, but not in liquid biopsy. In all patients, the disappearance of the T790M mutation during TKi therapy was related to disease progression. In 11 cases, modification of EGFR mutation status during treatment anticipated CT scan evidence of disease progression (median = three months). Conclusions: the liquid biopsy is an excellent resource. In our experience the liquid biopsy is the sensitive method of choice during treatment of advanced NSCLC patients. EGFR modification status during TKi therapy showed advanced disease progression.


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