Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving <i>EGFR</i>

Ha, Sang Yun; Choi, Seong Hee; Cho, Jong Ho; Choi, Heechul; Lee, Jinseon; Jung, Kyungsoo; Irwin, Darry; Liu, Xiao; Lira, Maruja E.; Mao, Mao; Kim, Hong Kwan; Choi, Yong Soo; Shim, Young Mog; Park, Woong-Yang; Choi, Yoon–La; Kim, Young Tae

doi:10.18632/oncotarget.2925

Cited by 120 publications

(86 citation statements)

References 41 publications

(42 reference statements)

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“…Notably, Asian LADC cohorts more frequently include females and never‐smokers than those of European descent . Consistent with this, EGFR mutation, which preferentially occurs in LADCs in females and never‐smokers, is more frequent in Asians than in US/European individuals .…”

Section: Egfr a Major Driver Oncogene In Asian Ladcsupporting

confidence: 63%

Gene aberrations for precision medicine against lung adenocarcinoma

Saito¹,

Shiraishi²,

et al. 2016

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Lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, is often triggered by an aberration in a driver oncogene in tumor cells. Examples of such aberrations are EGFR mutation and ALK fusion. Lung adenocarcinoma harboring such mutations can be treated with anticancer drugs that target the aberrant gene products. Additional oncogene aberrations, including RET,ROS1, and NRG1 fusions, skipping of exon 14 of MET, and mutations in BRAF,HER2,NF1, and MEK1, were recently added to the list of such “druggable” driver oncogene aberrations, and their responses to targeted therapies are currently being evaluated in clinical trials. However, approximately 30% and 50% of LADCs in patients in Japan and Europe/USA, respectively, lack the driver oncogene aberrations listed above. Therefore, novel therapeutic strategies, such as those that exploit the vulnerabilities of cancer cells with non‐oncogene aberrations, are urgently required. This review summarizes the current status of research on precision medicine against LADC and enumerates the research priorities for the near future.

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Section: Egfr a Major Driver Oncogene In Asian Ladcsupporting

confidence: 63%

Gene aberrations for precision medicine against lung adenocarcinoma

Saito¹,

Shiraishi²,

et al. 2016

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“…A head-to-head study is needed to define the value of the combination therapy in the patients with EGFR mutations. Previous studies have suggested that never smokers and Asian patients are more likely to harbour EGFR mutations and benefit more from EGFR-TKIs [32–33]. Furthermore, a history of never smoking was a significant independent predictor for survival in EGFR-TKI treatment [34].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

et al. 2016

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The role of a combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for non-small-cell lung cancer (NSCLC) has not been well established. To clarify this problem, we performed a meta-analysis with 15 studies identified from PubMed, EMBASE and the Cochrane Library. We found that the combined regimen had a significant benefit on progression-free survival (PFS) (hazard ratio (HR) = 0.80; 95% CI = 0.71–0.90; P < 0.001) and the objective response rate (ORR) (RR = 1.35; 95% CI = 1.14–1.59; P < 0.001). However, the combined regimen had no significant impact on overall survival (OS) (HR = 0.96; 95% CI = 0.90–1.03; P = 0.25). Subgroup analysis showed significantly higher OS advantages in EGFR mutation positive patients (P = 0.01), never smokers (P = 0.01), Asian patients (P = 0.02), patients receiving second-line treatment (P < 0.001), and those receiving a sequential combination of EGFR-TKIs and chemotherapy (P = 0.005). The combination regimen showed a higher incidence of grade 3–4 toxicities (leucopenia, neutropenia, febrile neutropenia, anemia, rash, fatigue and diarrhea). In summary, the combination of EGFR-TKIs plus chemotherapy in advanced NSCLC achieved a significantly longer PFS and a higher ORR but not longer OS. Well-designed prospective studies are needed to confirm these findings.

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“…Approximately 10–15% of Caucasian patients and 30–40% of Asian patients with non-small cell lung cancers (NSCLCs) harbor activating mutations in the epidermal growth factor receptor ( EGFR ) gene [1–3]. Analysis of tumors for these mutations has become standard of care [1, 2, 4].…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of resistance mutations detectable by next-generation sequencing in TKI-treated lung adenocarcinoma

et al. 2016

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EGFR-mutated lung adenocarcinomas routinely develop resistance to tyrosine kinase inhibitors (TKI). To better characterize the relative frequencies of the resistance mechanisms, we analyzed 48 EGFR-mutated TKI-resistant specimens from 41 patients. Next-generation sequencing of post-treatment specimens detected EGFR p.T790M in 31 (79%) of 39 patients, PIK3CA mutations in 10 (26%), EGFR p.S768_V769delinsIL in one, and KRAS p.G12C in one. Five PIK3CA mutations were outside of codons 542, 545, and 1047. Three of four pre-treatment specimens did not carry the PIK3CA mutation found in the post-treatment sample. Small cell carcinoma transformation was identified in four patients; none had p.T790M, including two where p.T790M was identified in the co-existing adenocarcinoma. In p.T790M-mutated specimens, the allele frequency was less than 5% in 24% of cases. p.T790M allele frequency was usually lower than that of the sensitizing mutation indicating that the resistance mutation was present either in a subset of cells or, if the sensitizing mutation was amplified, in a subset of the sensitizing alleles of a dominant clone. Eight patients had multiple resistance mutations, suggesting either multiple separate resistant clones or a single clone harboring multiple resistance mechanisms. PIK3CA mutations appear to be a more significant resistance mechanism than previously recognized.

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Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most often involving EGFR

Cited by 120 publications

References 41 publications

Gene aberrations for precision medicine against lung adenocarcinoma

Gene aberrations for precision medicine against lung adenocarcinoma

Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

Heterogeneity of resistance mutations detectable by next-generation sequencing in TKI-treated lung adenocarcinoma

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