Nationwide genomic screening network for the development of novel targeted therapies in advanced non-small cell lung cancer (LC-SCRUM-Japan).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8093-8093 ◽  
Author(s):  
Shingo Matsumoto ◽  
Kiyotaka Yoh ◽  
Takashi Seto ◽  
Takuma Yokoyama ◽  
Haruyasu Murakami ◽  
...  
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8518-8518 ◽  
Author(s):  
Haruyasu Murakami ◽  
Shigeki Umemura ◽  
Masahiro Shinoda ◽  
Masato Shingyoji ◽  
Yukari Ogawa ◽  
...  

8518 Background: Recent genomic studies of small-cell lung cancer (SCLC) have identified promising therapeutic strategies for this highly lethal form of cancer. Thus, we established a nationwide lung cancer genomic screening project in Japan (LC-SCRUM-Japan) to identify SCLC patients harboring targetable genomic alterations for the development of novel targeted therapies. Methods: The samples were subjected to a next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay, enabling the simultaneous analysis of 143 cancer-related genes. Results: As of December 2016, 133 institutions were participating and 295 patients had been enrolled. The median age was 69 years (range, 14-90 years). Two hundred seventeen (74%) were male and most patients (93%) were smokers. Among 268 samples completed analysis, we identified high prevalence of inactivating TP53/RB1 mutations in 198 (74%) /82 (31) of cases, respectively. MYC/MYCL1/MYCN amplifications were detected in 10 (4%) /13 (5) /4 (1) of cases, respectively. The NGS analysis also showed that 62 (23%) of cases had at least one targetable genomic alterations, including 7 EGFR activating mutations (3%), 6 KRAS activating mutations (2%), and 8 FGFR1 copy number gains (3%). No case was positive for ALK or ROS1 fusions. Never-smokers (71% vs. 5%, p<0.001) were significantly frequent in the EGFR type compared to the others. The KRAS type showed significantly poor progression free survival (PFS) of the first-line chemotherapy compared to the others (median PFS 1.2 vs. 6.1 months, respectively; p<0.001). Mutations in the PI3K/AKT/mTOR pathway were detected in 22 (8%) of the tumors: 10 PIK3CA mutations (4%), 9 PTEN inactivating mutations (3%) and 3 TSC2 inactivating mutations (1%). Among them, a case with PTEN mutation was enrolled in the investigator initiated phase II study of gedatolisib named “EAGLE-PAT” (UMIN 000020585). Conclusions: We identified a series of targetable genomic alterations in SCLC. This nationwide screening system is helpful for identifying targetable genomic alterations and their clinical features, contributing to the development of novel targeted therapies for this disease. Updated screening results will be presented at the 2017 ASCO Annual Meeting.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii204-ii204
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Behnam Sadeghirad ◽  
Jiawen Deng ◽  
Winston Hou ◽  
...  

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including &gt; 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25-554). All trials included adult patients with histologically proven NSCLC and &gt;1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3-799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3-254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7-289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5-167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.


2021 ◽  
Author(s):  
Hideko Isozaki ◽  
Ammal Abbasi ◽  
Naveed Nikpour ◽  
Adam Langenbucher ◽  
Wenjia Su ◽  
...  

2006 ◽  
Vol 1 (1) ◽  
pp. 13-22
Author(s):  
C. Gridelli ◽  
P. Maione ◽  
A. Rossi ◽  
C. Ferrara ◽  
G. Colantuoni ◽  
...  

2020 ◽  
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Yu-Chia Chen ◽  
Ting-Yuan Liu ◽  
Ya-Ting Lee ◽  
...  

Abstract Background: Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations. Method: We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients. Results: Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.Conclusions: We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.


CHEST Journal ◽  
2016 ◽  
Vol 150 (4) ◽  
pp. 723A
Author(s):  
Mickey Sachdeva ◽  
Prathamesh Prabhudesai ◽  
Valentine Ifeacho ◽  
Therese Santiago ◽  
Viola Zhu ◽  
...  

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