An Update on Predictive Biomarkers for Treatment Selection in Non-Small Cell Lung Cancer

Ahmadzada, Tamkin; Kao, Steven; Reid, Glen; Boyer, Michael; Mahar, Annabelle; Cooper, Wendy A.

doi:10.3390/jcm7060153

Cited by 50 publications

(43 citation statements)

References 63 publications

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“…In our study, we underlined the importance of niche mutations in terms of OS relative to the most frequent general somatic mutations and for KRAS in particular, which is considered to be the most frequent and aggressive mutation in lung adenocarcinoma. EGFR and KRAS gene mutations are already recorded in the molecular report that an oncologist needs to provide "personalized" therapy [ [17][18][19][20]. In addition to the mutations for which target therapies have been generally successful, for example, for the EGFR gene, there are still mutations without effective therapies, as for the KRAS and niche mutations.…”

Section: Discussionmentioning

confidence: 99%

Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study

et al. 2020

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Objective: In addition to the most common somatic lung cancer mutations (i. e., KRAS and EGFR mutations), other genes may harbor mutations that could be relevant for lung cancer. We defined BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations as "niche" mutations and analyzed. The aim of this retrospective cohort study was to assess the differences in the overall survival (OS) of patients with lung adenocarcinoma harboring niche somatic mutations. Results: Data were gathered for 252 patients. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that 1) niche mutations had a higher mortality than EGFR mutations (HR = 2.3; 95% CI = 1.2-4.4; p = 0.009); 2) KRAS mutations had a higher mortality than EGFR mutations (HR = 2.5; 95% CI = 1.4-4.5; p = 0.003); 3) niche mutations presented a similar mortality to KRAS mutations (HR = 0.9; 95% CI = 0.6-1.5; p = 0.797). Methods: Three cohorts of mutations were selected from patients with lung adenocarcinoma and their OS was compared. Mutations that were searched for, were 1) BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET; 2) K-RAS; and 3) EGFR. Differences in OS between these three cohorts were assessed by means of a multivariable Cox model that adjusted for age, sex, smoking habits, clinical stages, and treatments. Conclusions: Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations.

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Section: Discussionmentioning

confidence: 99%

Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study

et al. 2020

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“…Cytotoxic chemotherapy, usually platinum-based, the cornerstone of treatment for unselected patients for almost three https://doi.org/10.1016/j.lungcan.2019. 10 decades, is now challenged in many patients by targeted therapies and immune checkpoint inhibitors, and, in the near future, by chemo-immunotherapy [1]. Despite significant improvements in terms of treatment efficacy and tolerability, lung cancer, often diagnosed as advanced or metastatic disease, has a disappointing long term survival rate, remaining one of the first causes of cancer-related deaths among both men and women [2].…”

Section: Introductionmentioning

confidence: 99%

Quality of life analysis in lung cancer: A systematic review of phase III trials published between 2012 and 2018

et al. 2020

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“…There is still a lack of good prognostic biomarkers for response. PD-L1 expression and high mutational burden/neoantigen load have emerged as the most promising ones, but the absence of these has not been able to predict lack of response (Ahmadzada et al, 2018). The aim of this study was to achieve more knowledge about the immune microenvironment in NSCLC and how it influences risk of relapse after surgery, with the hope that this could help selecting patients for adjuvant immunotherapy and guide the development of new treatment options.…”

Section: Introductionmentioning

confidence: 99%

The immune microenvironment in non‐small cell lung cancer is predictive of prognosis after surgery

et al. 2019

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The impact of the tumor immune microenvironment on overall survival in non‐small cell lung cancer ( NSCLC ) has been studied, but there is little information on its relevance for risk of relapse after surgery. Understanding more about the immune microenvironment in previously untreated NSCLC could help in identifying high‐risk patients and patients more likely to benefit from neoadjuvant/adjuvant immunotherapy. Here, we examined gene expression in 399 surgically derived NSCLC samples and 47 samples from normal lung, using Agilent microarray and RNA sequencing. In 335 of the tumor samples, programmed death‐ligand 1 ( PD ‐L1) expression was evaluated by immunohistochemistry. Gene expression was used to estimate content of immune cells and to calculate an immune score. Properties of the immune microenvironment, and its impact on prognosis, were compared in histological subgroups and gene expression subtypes. Tumors with an active immune microenvironment were found for both adenocarcinomas ( AD ) and squamous cell carcinomas ( SCC ). In AD , high immune score and high estimates of several immune cell types belonging to the adaptive immune system were associated with better progression‐free survival ( PFS ), while in SCC , no association between immune characteristics and PFS was found. The immune microenvironment, including PD ‐L1 expression, and its impact on prognosis showed clear differences in AD and SCC gene expression subtypes. In conclusion, the NSCLC immune microenvironment is predictive of prognosis after surgery. Lung AD and SCC gene expression subtypes should be investigated as potential prognostic biomarkers in patients treated with immune checkpoint inhibitors.

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An Update on Predictive Biomarkers for Treatment Selection in Non-Small Cell Lung Cancer

Cited by 50 publications

References 63 publications

Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study

Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study

Quality of life analysis in lung cancer: A systematic review of phase III trials published between 2012 and 2018

The immune microenvironment in non‐small cell lung cancer is predictive of prognosis after surgery

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