Epidermal Growth Factor Receptor (EGFR) Mutations and Anaplastic Lymphoma Kinase/Oncogene or C-Ros Oncogene 1 (ALK/ROS1) Fusions Inflict Non-Small Cell Lung Cancer (NSCLC) Female Patients Older Than 60 Years of Age

Li, Ke; Xu, Meiqing; Jiang, Xianliang; Sun, Xiaohui

doi:10.12659/msm.911333

Cited by 13 publications

(10 citation statements)

References 23 publications

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“…Consistently, we observed such correlation in our study, indicating that the high frequency of KRAS mutation in our cohort could be attributable to high prevalence of smoking in Vietnam population. In addition, we found that ALK and ROS1 rearrangement mutations were more common in younger patients as compared to elderly patients, which is consistent with previous studies 28,29 . Take together, our data revealed several significant correlations between driver gene mutation prevalence and patients' clinical characteristics.…”

Section: Discussionsupporting

confidence: 92%

“…www.nature.com/scientificreports www.nature.com/scientificreports/ Correlation between mutation prevalence and clinicopathological features of Vietnamese NSCLC patients. Previous studies have reported significant association between prevalence of driver mutations and patients' clinicopathological features [24][25][26][27][28][29] . However, the results are often inconsistent across different studies.…”

Section: Comparison Of Mutation Profiles Among Three Nsclc Cohorts Tmentioning

confidence: 99%

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Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population

Dang

Tran²,

Tran³

et al. 2020

Sci Rep

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Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts. Lung cancer is the most common malignancy and the leading cause of cancer related deaths worldwide (18.4% of total cancer deaths), with non-small cell lung cancer (NSCLC) being the most common subtype, accounting for approximately 85% of all diagnosed cases 1,2. The majority of NSCLC patients display advanced disease when diagnosed and thus have poor prognosis 2,3. It is well established that acquired genetic alterations in certain driver genes result in tumour growth and invasiveness, and that patients harboring certain mutations may benefit from targeted therapies 4,5. Indeed, a randomized clinical trial reported that advanced NSCLC patients harboring activating mutations in EGFR, one of the major driver genes of NSCLC, exhibited longer progression-free period when treated with a tyrosine kinase inhibitor (TKI), gefitinib, compared to those treated with standard platinum based chemotherapy 6. However, those who were treated with TKI drugs can acquire secondary resistant mutations, in which case a new treatment regimen is needed to maintain therapeutic effect 7,8. In addition to EGFR, NSCLC patients carrying ALK or ROS1 rearrangement were shown to respond well to a different TKI drug,

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Section: Discussionsupporting

confidence: 92%

Section: Comparison Of Mutation Profiles Among Three Nsclc Cohorts Tmentioning

confidence: 99%

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population

Dang

Tran²,

Tran³

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In addition, recent studies showed that 69% and 65.8% were male patients (9,11). Ke et al reported that the percentage of women was significantly higher in patients younger than 60 years compared to those older than 60 years (28). In our study, 84 (65.1%) of the 129 patients were female.…”

Section: Discussionsupporting

confidence: 58%

Clinicopathological Features in Elderly ALK-rearranged Non-small Cell Lung Cancer Patients

Miyazaki¹,

Sato²,

Kodama³

et al. 2020

In Vivo

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Aim: To clarify the clinicopathological features in elderly anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) patients. Patients and Methods: A retrospective study was performed in 129 ALK rearranged NSCLC patients diagnosed between April 2008 and March 2019 in fifteen Institutions of the Ibaraki prefecture, Japan. Results: Median age of patients was 63 years. In 59 patients aged 65 and older, the proportions of patients with advanced stage and those treated with ALKtyrosine kinase inhibitor (TKI) were lower than those younger than 65 years. There was no difference in overall survival (OS) between the two age groups. Among the elderly patients, no difference was observed in OS between the patients aged 65-69 and those aged 70 and older. In 89 patients treated with TKI, no significant differences were observed in the progression-free survival of TKIs and OS between patients aged 65 and older and those younger than 65, respectively. Conclusion: Evaluation of ALK gene status and TKI treatment are desirable even for elderly patients. Advances in molecular biology have led to discovery of specific driver genes in certain cancer types and therefore to development of specific therapeutics (1, 2). This new trend is evident in the clinical practice of NSCLC patients. Mutations in the anaplastic lymphoma kinase (ALK) fusion gene is one such driver gene. Long-term survival can be expected in ALKrearranged NSCLC patients, but its frequency is very rare (1, 2001 This article is freely accessible online.

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“…Resistance to therapy is a major clinical issue contributing to poor prognosis [2]. Non-small-cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers [3,4]. In 2016, Sweden recorded 4108 new lung cancer cases; 3677 patients died from the disease in that year [5,6].…”

Section: Introductionmentioning

confidence: 99%

The Cost-Effectiveness of Lorlatinib Versus Chemotherapy as a Second- or Third-Line Treatment in Anaplastic Lymphoma Kinase (ALK)-Positive Non-small-cell Lung Cancer in Sweden

et al. 2021

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Background Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-rearranged non-small-cell lung cancer (NSCLC) previously treated with a second-generation ALK inhibitor or with first-and second-generation ALK inhibitors. We examined the cost-effectiveness of second-or third-line+ (2L+ or 3L+) lorlatinib in Sweden, versus chemotherapy. Methods A partitioned survival model with three health states (progression free, progressed, or death) was used. Lorlatinib relative efficacy versus chemotherapy was derived using unanchored matching adjusted indirect treatment comparisons from a phase 2 clinical trial. Utility data were derived from the same trial and published studies. Costs (year 2019) were obtained from Swedish national data. Costs and benefits were discounted at 3% per annum using a societal perspective (base case). Model robustness was evaluated with deterministic and probabilistic sensitivity analyses. Results For 2L+, the average discounted total quality-adjusted life year (QALY) gain was 1.29 years. Total incremental costs were Swedish krona (SEK) 731,791, resulting in an incremental cost-effectiveness ratio (ICER) of SEK 566,278 per QALY gained. Non-discounted survival gain amounted to 1.94 years. For 3L+, the average discounted total QALY gain was 1.25 years. Total incremental costs were SEK 754,801, resulting in an ICER of SEK 603,934 per QALY gained. Nondiscounted survival gain was 1.88 years. Sensitivity analyses were consistent. Conclusions ICERs ranged from SEK 421,000 to SEK 384,066 less than the boundary for a cost-effective treatment for a high-severity disease in Sweden (SEK 988,000), suggesting 2L+ or 3L+ lorlatinib is a cost-effective treatment for ALKpositive NSCLC versus chemotherapy.

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Epidermal Growth Factor Receptor (EGFR) Mutations and Anaplastic Lymphoma Kinase/Oncogene or C-Ros Oncogene 1 (ALK/ROS1) Fusions Inflict Non-Small Cell Lung Cancer (NSCLC) Female Patients Older Than 60 Years of Age

Cited by 13 publications

References 23 publications

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population

Clinicopathological Features in Elderly ALK-rearranged Non-small Cell Lung Cancer Patients

The Cost-Effectiveness of Lorlatinib Versus Chemotherapy as a Second- or Third-Line Treatment in Anaplastic Lymphoma Kinase (ALK)-Positive Non-small-cell Lung Cancer in Sweden

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