ALK rearrangement testing and treatment patterns for patients with ALK-positive non-small cell lung cancer

Guérin, Annie; Sasané, Medha; Zhang, Jie; Macalalad, Alexander R.; Galebach, Philip; Jarvis, John; Kageleiry, Andrew; Culver, Kenneth W.; Wu, Eric Q.; Wakelee, Heather A.

doi:10.1016/j.canep.2015.04.005

Cited by 21 publications

(15 citation statements)

References 15 publications

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“…It is important to note that these studies have not directly addressed the frequency of such alterations by age group given the rarity of young patients with NSCLC. 27–29 …”

Section: Discussionmentioning

confidence: 99%

“…21,22,26 More recent studies of the incidence of EGFR mutations and ALK rearrangements have suggested that age may not be as significant of a predictor of mutation status as previously surmised. 27–29 However, studying the relationship between age and genotype in young patients is challenging given the presence of multiple confounding factors including smoking status, sex and race. 19,20,28–33 The relative rarity of young NSCLC patients in the aforementioned studies and the low incidence of many of these targetable genomic alterations further complicates the study of this association.…”

Section: Introductionmentioning

confidence: 99%

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Association Between Younger Age and Targetable Genomic Alterations and Prognosis in Non–Small-Cell Lung Cancer

et al. 2016

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Importance NSCLC in the young is a rare entity and the genomics and clinical characteristics of this disease are poorly understood. In contrast, young age at diagnosis has been demonstrated to define unique disease biology in other cancers. Here we report on the association of young age with targetable genomic alterations and prognosis in a large cohort of NSCLC patients. Objective To determine the relationship between young age at diagnosis and both the presence of a potentially targetable genomic alteration as well as prognosis and natural history. Design All patients with NSCLC genotyped at the Dana-Farber Cancer Institute between 2002–2014 were identified. Tumor genotype, patient characteristics and clinical outcomes were collected. Multivariate logistic regression was used to analyze the relationship between age and mutation status. Multivariate Cox proportional hazard models were fitted for survival analysis. Setting A National Cancer Institute (NCI) designated comprehensive cancer center. Participants All patients with NSCLC seen at the Dana-Farber Cancer Institute between 2002–2014 who underwent tumor genotyping. Main Outcome Measure The frequency of targetable genomic alterations by defined age categories as well as the association of these age groups with survival. Results 2237 patients with NSCLC were studied. EGFR (p=0.02) and ALK (P<0.01) were associated with younger age, and a similar trend existed for HER2 (p=0.15) and ROS1 (p=0.1) but not BRAF V600E (p=0.43). Amongst patients tested for all 5 targetable genomic alterations, younger age was associated with an increased frequency of a targetable genotype (p<0.01). Those diagnosed at age 50 or younger have a 59% increased likelihood of harboring a targetable genotype. While presence of a potentially targetable genomic alteration treated with a targeted agent was associated with improved survival, the youngest and oldest age groupings had similarly poor outcomes even when a targetable genotype was present. Conclusion & Relevance Younger age is associated with an increased likelihood of harboring a targetable genotype and is an underappreciated clinical biomarker in NSCLC. The survival of young NSCLC patients is unexpectedly poor compared to other age groups, suggesting more aggressive disease biology. These findings underscore the importance of comprehensive genotyping including NGS in younger patients with lung cancer.

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“…It is important to note that these studies have not directly addressed the frequency of such alterations by age group given the rarity of young patients with NSCLC. 27–29 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association Between Younger Age and Targetable Genomic Alterations and Prognosis in Non–Small-Cell Lung Cancer

et al. 2016

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“…This cohort of patients was previously described in more detail. 18 For the current study, patients who had initiated and discontinued crizotinib monotherapy were selected for further analysis.…”

Section: Sample Selectionmentioning

confidence: 99%

Treatment, overall survival, and costs in patients withALK-positive non-small-cell lung cancer after crizotinib monotherapy

Guérin

Sasané

Wakelee

et al. 2015

Current Medical Research and Opinion

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“…30,35,181,215,216 Although other studies have indicated that these findings may reflect testing bias, 217 the documentation of an association between younger patient age and an actionable biomarker is another consideration in selecting patients for testing. The boundary between young and not young is not well defined, however, and a clear evidence-based cutoff for this guideline cannot be established.…”

Section: Expert Consensus Opinionmentioning

confidence: 99%

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

Aung

Donald

Ellison

et al. 2014

The Journal of Molecular Diagnostics

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Context: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. Objective: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. Design: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. Results: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. Conclusions: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of

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ALK rearrangement testing and treatment patterns for patients with ALK-positive non-small cell lung cancer

Cited by 21 publications

References 15 publications

Association Between Younger Age and Targetable Genomic Alterations and Prognosis in Non–Small-Cell Lung Cancer

Association Between Younger Age and Targetable Genomic Alterations and Prognosis in Non–Small-Cell Lung Cancer

Treatment, overall survival, and costs in patients withALK-positive non-small-cell lung cancer after crizotinib monotherapy

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

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