scholarly journals Cardiac Safety Assessment of Lazertinib: Findings From Patients With EGFR Mutation-Positive Advanced NSCLC and Preclinical Studies

2021 ◽  
Vol 2 (10) ◽  
pp. 100224 ◽  
Author(s):  
Seong Bok Jang ◽  
Kyeong Bae Kim ◽  
Sujin Sim ◽  
Byoung Chul Cho ◽  
Myung-Ju Ahn ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2425
Author(s):  
Paolo Bironzo ◽  
Maria Lucia Reale ◽  
Tessa Sperone ◽  
Fabrizio Tabbò ◽  
Andrea Caglio ◽  
...  

Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation-positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co-alterations may predict different outcomes to TKIs. Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first-line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD-L1 expression was also evaluated. Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; p = 0.088), PFS (mPFS 10.9 vs. 11.2 months; p = 0.415) and ORR (55.9% vs. 68.1%; p = 0.202) were observed comparing patients without and with co-alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD-L1 expression levels by co-mutational status were found. Significant associations with presence of co-alterations and younger age (p = 0.018) and baseline lymph nodes metastases (p = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, p = 0.011). Conclusions: Pathogenic co-alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.


2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.


2017 ◽  
Vol 12 (11) ◽  
pp. S2088
Author(s):  
O. Macedo-Pérez ◽  
I. Lyra-González ◽  
D. Marroquín-Flores ◽  
G. Cruz-Rico ◽  
L. Ramírez-Tirado ◽  
...  

Author(s):  
Jun-ichi Okada ◽  
Takashi Yoshinaga ◽  
Junko Kurokawa ◽  
Takumi Washio ◽  
Tetsushi Furukawa ◽  
...  

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

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8069-8069
Author(s):  
J. Z. Wang ◽  
T. T. An ◽  
L. Yang ◽  
H. Bai ◽  
J. Zhao ◽  
...  

8069 Background: To compare therapeutic effects of immediate vs. delayed gefitinib used for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after front-line chemotherapy in Chinese population. Methods: The study included 121 Chinese with advanced NSCLC treated with standard chemotherapy and obtained DC followed by either immediate gefitinib (66 cases) or delayed gefitinib, i.e. when tumors progressed (55 cases). The disease control rate (DCR), median progression-free survival time (PFS), median overall survival time (OS) of the two groups were analyzed. The impact of EGFR mutation status on the treatments was also evaluated. Results: The median PFS of patients treated in the immediate treatment setting was significantly longer than that of patients without gefitinib treatment (15.23 months versus 8.13 months,P<0.001). However, the overall median PFS was similar in patients treated with either immediate or delayed settings (15.23 months and 16.23 months respectively, P=0.450). There was no significant difference in OS between the two groups. Although patients whose tumors had EGFR mutation showed a longer median PFS compared to those without the mutation in both treatment groups, similar overall PFS was observed between the groups for patients with EGFR mutation (18.75 months and 18.30 months for maintenance and second-line groups, respectively). Conclusions: Immediate gefitinib use may improve PFS for Chinese patients with advanced NSCLC after front-line chemotherapy. However, similar PFS may be achieved by delayed use of gefitinib. No significant financial relationships to disclose.


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