Hybrid Capture-Based Comprehensive Genomic Profiling Identifies Lung Cancer Patients with Well-Characterized Sensitizing Epidermal Growth Factor Receptor Point Mutations That Were Not Detected by Standard of Care Testing

Suh, James; Schrock, Alexa B.; Johnson, Adrienne; Lipson, Doron; Ramkissoon, Shakti; Vergilio, Jo‐Anne; Elvin, Julia A.; Shakir, Abdur; Ruehlman, Peter; Reckamp, Karen L.; Ou, Sai‐Hong Ignatius; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.; Ali, Siraj M.

doi:10.1634/theoncologist.2017-0493

Cited by 11 publications

(11 citation statements)

References 22 publications

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“…The patients with NSCLC with EGFR mutation may benefit from treatment using EGFR TKIs. In this study, the two most common EGFR mutations identified in Chinese patients with NSCLC were exon 19 deletion (36.7%) and L858R mutation (33.4%), which are sensitive to EGFR TKIs, and this was consistent with the findings of the study published with Western people as the main subjects . The exon 20 insertions, which were mostly insensitive to EGFR TKIs , amounted to 3.8% of EGFR mutations, and the most common resistant mutation, T790M , accounted for 5.5% of EGFR mutations.…”

Section: Discussionsupporting

confidence: 89%

“…For those 5.5% of patients with primary EGFR T790M mutation, which suggests primary resistance, selecting one of the third‐generation EGFR TKIs as first‐line therapy is advisable. NGS is currently the most effective way to detect EGFR gene alterations . By increasing the depth of sequencing, some less common and low‐frequency mutations may be discovered.…”

Section: Discussionmentioning

confidence: 99%

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Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

Dai

Wang

et al. 2019

The Oncologist

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Background Non‐small cell lung cancer (NSCLC) is one of the most common human malignancies and the leading cause of cancer‐related death. Over the past few decades, genomic alterations of cancer driver genes have been identified in NSCLC, and molecular testing and targeted therapies have become standard care for lung cancer patients. Here we studied the unique genomic profile of driver genes in Chinese patients with NSCLC by next‐generation sequencing (NGS) assay. Materials and Methods A total of 1,200 Chinese patients with NSCLC were enrolled in this study. The median age was 60 years (range: 26–89), and 83% cases were adenocarcinoma. NGS‐based genomic profiling of major lung cancer‐related genes was performed on formalin‐fixed paraffin‐embedded tumor samples and matched blood. Results Approximately 73.9% of patients with NSCLC harbored at least one actionable alteration recommended by the National Comprehensive Cancer Network guideline, including epidermal growth factor receptor (EGFR), ALK, ERBB2, MET, BRAF, RET, and ROS1. Twenty‐seven patients (2.2%) harbored inherited germline mutations of cancer susceptibility genes. The frequencies of EGFR genomic alterations (both mutations and amplification) and ALK rearrangement were identified as 50.1% and 7.8% in Chinese NSCLC populations, respectively, and significantly higher than the Western population. Fifty‐six distinct uncommon EGFR mutations other than L858R, exon19del, exon20ins, or T790M were identified in 18.9% of patients with EGFR‐mutant NSCLC. About 7.4% of patients harbored both sensitizing and uncommon mutations, and 11.6% of patients harbored only uncommon EGFR mutations. The uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. In patients <40 years of age, the ALK‐positive percentage was up to 28.2%. Moreover, 3.2% of ALK‐positive patients harbored multi ALK rearrangements, and seven new partner genes were identified. Conclusion More unique features of cancer driver genes in Chinese NSCLC were identified by next‐generation sequencing. These findings highlighted that NGS technology is more feasible and necessary than other molecular testing methods, and suggested that the special strategies are needed for drug development and targeted therapy for Chinese patients with NSCLC. Implications for Practice Molecular targeted therapy is now the standard first‐line treatment for patients with advanced non‐small cell lung cancer (NSCLC). Samples of 1,200 Chinese patients with NSCLC were analyzed through next‐generation sequencing to characterize the unique feature of uncommon EGFR mutations and ALK fusion. The results showed that 7.4% of EGFR‐mutant patients harbored both sensitizing and uncommon mutations and 11.6% harbored only uncommon mutations. Uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. ALK fusion was more common in younger patients, and the frequency decreased monotonically with age. 3.2% of ALK‐positive patien...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

Dai

Wang

et al. 2019

The Oncologist

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“… 5 The expanded use of NGS found in the present study may have resulted in the increase in the incidence of EGFRex20ins observed between 2011 and 2020, as NGS has an improved ability to identify rare EGFR variants, including EGFRex20ins. 16 , 17 , 18 In a study comparing EGFR detection rates using comprehensive genomic profiling (CGP), an NGS approach, and PCR in 103 cases with confirmed previous EGFR test results, CGP identified 22 patients (21%) with sensitizing EGFR point mutations that were not detected by PCR, including four of seven patients (57%) with EGFR exon 20 mutations. 18 A real-world study using genomic databases to analyze the ability of PCR and NGS to comprehensively identify EGFRex20ins revealed that PCR methods are projected to miss 50% or more of EGFRex20ins, whereas NGS is more likely to detect the full range of EGFRex20ins variants.…”

Section: Discussionmentioning

confidence: 99%

EGFR Testing Patterns and Detection of EGFR Exon 20 Insertions in the United States

Lin

Yang

Crossland

et al. 2022

JTO Clinical and Research Reports

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“…However, FISH testing for these genes, unlike RNA-based NGS testing, has been shown to be at risk for false positives [4], and may under-report actionable alterations that could result in denying patients treatment with these highly efficacious TKI inhibitors [5, 6]. Similarly, CGP can detect highly actionable EGFR mutations that predict response to EGFR inhibitors in NSCLC that have been missed by single gene testing [7].…”

Section: Introductionmentioning

confidence: 99%

Oncologist uptake of comprehensive genomic profile guided targeted therapy

Nesline¹,

DePietro²,

et al. 2019

Oncotarget

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We describe the extent to which comprehensive genomic profiling (CGP) results were used by oncologists to guide targeted therapy selection in a cohort of solid tumor patients tested as part of standard care at Roswell Park Comprehensive Cancer Center June 2016–June 2017, with adequate follow up through September 2018 ( n = 620). Overall, 28.4% of CGP tests advised physicians about targeted therapy use supported by companion diagnostic or practice guideline evidence. Post-test targeted therapy uptake was highest for patients in active treatment at the time of order (86% versus 76% of treatment naïve patients), but also took longer to initiate (median 50 days versus 7 days for treatment naïve patients), with few patients (2.6%) receiving targeted agents prior to testing. 100% of patients with resistance variants did not receive targeted agents. Treatment naïve patients received immunotherapy as the most common alternative. When targeted therapy given off-label or in a trial was the best CGP option, (7%) of patients received it. Our data illustrate the appropriate and heterogeneous use of CGP by oncologists as a longitudinal treatment decision tool based on patient history and treatment needs, and that some patients may benefit from testing prior to initiation of other standard treatments.

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Hybrid Capture-Based Comprehensive Genomic Profiling Identifies Lung Cancer Patients with Well-Characterized Sensitizing Epidermal Growth Factor Receptor Point Mutations That Were Not Detected by Standard of Care Testing

Cited by 11 publications

References 22 publications

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

Genomic Signature of Driver Genes Identified by Target Next-Generation Sequencing in Chinese Non-Small Cell Lung Cancer

EGFR Testing Patterns and Detection of EGFR Exon 20 Insertions in the United States

Oncologist uptake of comprehensive genomic profile guided targeted therapy

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