Progression patterns at RECIST PD during EGFR-TKIs in advanced NSCLC patients harboring EGFR mutation.

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 12 (11) ◽  
pp. S2088
Author(s):  
O. Macedo-Pérez ◽  
I. Lyra-González ◽  
D. Marroquín-Flores ◽  
G. Cruz-Rico ◽  
L. Ramírez-Tirado ◽  
...  

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.


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.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yujia Wang ◽  
Guoyu Wu ◽  
Ru Li ◽  
Yingzhe Luo ◽  
Xingmei Huang ◽  
...  

Objective: To explore the efficacy comparison between epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) combined with traditional Chinese medicine (TCM) and single EGFR-TKIs for advanced non-small cell lung cancer (NSCLC).Methods: A total of 91 NSCLC patients with EGFR mutation were divided into an experimental group and a control group (in a ratio of 2:1) to receive TCM and EGFR-TKIs (61 cases) or single EGFR-TKIs (30 cases). Patients in the control group took EGFR-TKIs and those in the experimental group took EGFR-TKIs plus TCM. We analyzed the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events of two groups.Results: The mPFS of the experimental group and the control group was 12.3 and 8.9 months (P = 0.02), respectively, and the mOS of the experimental group and the control group was 28.2 and 24.2 months (P = 0.02), respectively. Subgroup analysis showed that for the patients with exon 19 deletion mutation (19DEL), mPFS between experimental group and control group was 12.7 and 10.1 months, respectively (P = 0.12). For exon 21 deletion mutation (L858R), the PFS of two groups was 10.8 vs. 8.2 months, respectively (P = 0.03). The subgroup analysis also showed that, for the patients with exon 19 deletion mutation, mOS between the experimental group and the control group was 30.3 and 28.7 months, respectively (P = 0.19). For exon 21 deletion mutation, the mOS of two groups was 25.5 vs. 21.3 months, respectively (P = 0.01). The DCR of the experimental group and the control group was 93.3% and 80.1%, respectively (P = 0.77). Grade 3–4 treatment-related adverse events were less common with the experimental group (11.48%) than the control group (26.67%).Conclusion: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM had a certain effect to prolong mPFS and mOS, compared with the use of EGFR-TKIs alone, especially for the patients with L858R. This conclusion has a significant effect on improving the survival of NSCLC patients after EGFR-TKIs resistance. It deserves further study.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7540-7540
Author(s):  
Shigehiro Yagishita ◽  
Hidehito Horinouchi ◽  
Tomoko Taniyama ◽  
Shinji Nakamichi ◽  
Satoru Kitazono ◽  
...  

7540 Background: EGFR mutational status is an important biomarker in advanced NSCLC patients. However, little is known about the frequency and clinical significance of the presence of EGFR mutation in patients with potentially curable locally advanced NSCLC (LA-NSCLC) eligible for definitive chemoradiotherapy (CRT). Methods: Between Jan 2001 and Dec 2010, we conducted analysis for the presence of EGFR mutations, in consecutive NSCLC patients who were eligible for CRT. The response rate (RR), progression-free survival (PFS), 2-year relapse-free rate, first relapse sites, and overall survival were investigated according to the EGFR mutational status. Results: A total of 528 patients received CRT at the National Cancer Center Hospital during the study period. Of these, 274 were diagnosed as having non-squamous NSCLC, and sufficient specimens for mutational analyses could be obtained from 145 patients. EGFR mutants (EGFR-mt) were found at a frequency of 18% in these patients. In addition to the well-known characteristics of NSCLC patients carrying EGFR mutations (female, adenocarcinoma, and never/ light smoker), the proportion of cases with smaller (T1/2) primary lesions was higher in patients with EGFR-mt than in those carrying wild-type EGFR (EGFR-wt). EGFR-mt showed a slightly better RR (85.7% vs. 72.9%), but similar median PFS (12.2 m vs. 10.6 m) and 2-year relapse free rates (23.8% vs. 29.2%) as compared to EGFR-wt. Local recurrence as first relapse occurred less frequently in EGFR-mt than in EGFR-wt (6% vs. 20%). After disease progression, a majority of EGFR-mt received EGFR-TKIs (62%), and these patients showed longer post-progression survival and a higher 5 year survival rate (60% vs. 40%) than EGFR-wt. Conclusions: Among the LA-NSCLC patients eligible for definitive CRT analyzed, 18% had EGFR- activating mutations. Although definitive CRT was similarly effective in both EGFR-mt and EGFR-wt, slightly better local control rate was noted in EGFR-mt. Treatment with EGFR-TKIs contributed to longer post-progression survival and overall survival in LA-NSCLC patients harboring EGFR mutations.


2019 ◽  
Vol 14 (10) ◽  
pp. S846
Author(s):  
L.A. Ramírez Tirado ◽  
S. Guzmán ◽  
C. Goycochea-Robles ◽  
F. Barrón ◽  
L. Cabrera-Miranda ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19136-e19136
Author(s):  
Shuhang Wang ◽  
Jie Wang ◽  
Hua Bai ◽  
Tongtong An ◽  
Jun Zhao ◽  
...  

e19136 Background: EGFR mutation is a strong predictor of EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitor) therapy in advanced NSCLC. However, 20-30% of patients with EGFR mutation are resistant to EGFR-TKIs, suggesting that other determinants of outcome beyond EGFR mutation might exist. We hypothesized that plasma microRNA (miRNA) might play a role. Methods: Training group: 20 advanced NSCLC patients treated with EGFR-TKIs as first-line therapy with EGFR 19 deletion mutation were enrolled, 10 of whom responded dramatically while other 10 are resistant. Matched plasma were collected for miRNA profile detection using TaqMan Low-Density (TLDA). Testing group: Real-time PCR were employed to identify the level of miRNAs found significant differently expressed in training step; bioinformatics was applied to find related miRNAs possibly account for resistance. Validation group: Another cohort with EGFR 19 deletion mutation present dramatically different response to EGFR-TKI was used to analyze the difference of miRNAs expression between responding and resistant group. Results: Training group: 153 miRNAs were found differently expressed between responding and resistant group. Testing group: 3 miRNAs (miR-21, AmiR-27a, and miR-218) were verified significantly higher (P=0.004, A0.009, A0.041, respectively) in resistant group than responding group. Validation group: expression level of these 3 miRNAs was validated to be significantly different (P=0.011, A0.011, A0.026, respectively) between 17 couples advanced NSCLC patients with different response to EGFR-TKI. Conclusions: Higher expression level of miR-21, AmiR-27a, and miR-218 might play the role in the resistance to EGFR-TKI for advanced NSCLC patients who had an EGFR exon 19 deletion mutation treated with EGFR-TKI, which needs further validation.


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