Genomic testing among patients with newly diagnosed advanced non-small cell lung cancer in the United States: A contemporary clinical practice patterns study

Paz‐Ares, Luis; Gondos, Ádám; Saldaña, Diego; Thomas, Marlène; Mascaux, Céline; Bubendorf, Lukas

doi:10.1016/j.lungcan.2022.01.021

Cited by 21 publications

(17 citation statements)

References 38 publications

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“…Multiple “hotspot” assays can quickly exhaust available tissue and lead to false negatives due to tissue depletion [ 21 , 29 , 39 , 42 – 44 ]. A recent study of advanced NSCLC found that NGS panels had a 39% lower rate of unsuccessful genotyping, resulting in 30% fewer missed treatment opportunities compared to non-NGS assays [ 18 ]. Although NGS may take several weeks to process, rapid EGFR testing workflows have been reported and allow treatment with EGFR -directed therapies within days, all without compromising NGS workflows [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Molecular testing (also referred to as biomarker testing, genomic analysis, molecular profiling, or molecular analysis) of lung needle biopsy specimens is crucial for identifying subsets of patients who are candidates for targeted therapy or immunotherapy. Despite recommendations by the National Comprehensive Cancer Network (NCCN) for molecular testing in all cases of advanced NSCLC [ 6 ], testing levels and results remain suboptimal [ 2 , 16 , 17 ], which translates to missed treatment opportunities [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Optimizing molecular testing of lung cancer needle biopsy specimens: potential solutions from an interdisciplinary qualitative study

et al. 2023

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Background Molecular testing can detect actionable genomic alterations and tumor cell surface proteins in patients with non–small cell lung cancer (NSCLC). However, utilization remains suboptimal, representing missed treatment opportunities. This study aimed to identify challenges and potential solutions to obtaining percutaneous lung needle biopsy specimens for successful molecular testing in patients with advanced NSCLC. Methods This interdisciplinary qualitative study included ten radiologists and four pathologists from academic and community settings across the United States who routinely perform and analyze percutaneous lung needle biopsies. Participants underwent semi-structured one-on-one interviews (Phase 1). Interview questionnaires were constructed based on a literature review of key lines of inquiry and conducted by professional market researchers using the theoretical domains framework. Primary barriers to molecular testing were identified using thematic analysis. Subsequently, multidisciplinary focus groups were convened to identify potential solutions (Phase 2). Results Four themes emerged as barriers to molecular testing and were matched to the clinical workflow: (1) biopsy request, (2) biopsy procedure, (3) specimen analysis, and (4) communication. The nineteen potential solutions included adding a “checkbox” to indicate molecular testing in the biopsy request, leveraging pre-procedural imaging to guide biopsies, conserving tissue through appropriate allocation strategies and next generation sequencing panels instead of sequential single-gene assays, instituting reflex-molecular testing upon NSCLC diagnosis, tracking and communicating biopsy outcomes at multidisciplinary tumor boards, and improving integration of radiologists and pathologists into oncology care teams. Conclusions Potential solutions exist to increase successful molecular testing of lung needle biopsy specimens in patients with advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimizing molecular testing of lung cancer needle biopsy specimens: potential solutions from an interdisciplinary qualitative study

et al. 2023

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“…BRAF mutations can be detected both by PCR or IHC methods, although these techniques are commonly limited to BRAF V600E‐mutation detection, in contrast to NGS testing, which includes multiple gene panels capable of evaluating V600E and non‐V600E mutations. Although BRAF analysis is considered a minimum requirement for NSCLC diagnosis, it has been reported that these have only been tested in approximately one half of patients when diagnosed using non‐NGS techniques 11 …”

Section: Driver Alterations In Nsclcmentioning

confidence: 99%

Targeted therapy for lung cancer: Beyond EGFR and ALK

Herrera-Juárez

Serrano-Gómez

Bote-de-Cabo

et al. 2023

Cancer

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Precision oncology comprises the set of strategies that aim to design the best cancer treatment based on tumor biology. A recognized subset of patients with nonsmall cell lung cancer (NSCLC) harbor actionable genomic aberrations that can benefit from targeted therapy. In lung cancer, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are well characterized oncogenic drivers for which the therapeutic use of tyrosine kinase inhibitors has demonstrated improved outcomes compared with chemotherapy.Other druggable targets are also well characterized, and effective inhibitors have been developed and commercialized, leading to a paradigm shift in NSCLC treatment. Here, the authors provide a review of the oncogenic role of the most relevant molecular alterations in NSCLC and emerging treatments in this setting beyond EGFR-driven and ALK-driven diseases. K E Y W O R D Sdriver mutations, genomic aberrations, nonsmall cell lung cancer (NSCLC), targeted therapy, tyrosine kinase inhibitors (TKI) 18.9 months with osimertinib versus 10.2 months with firstgeneration EGFR inhibitors (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.37-0.57) 6 in patients with EGFR-mutant NSCLC and 37.8 months with alectinib versus 23.0 months with crizotinib, respectively (HR, 0.43; 95% CI, 0.32-0.58), 7 in those with ALK-driven NSCLC. This has guided a consecutive generation of TKIs to regulatory approval and has established them as the standard of care for patients with EGFR-mutant and ALK-rearranged tumors in the first-line context for advanced NSCLC.

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“…2 Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. 3 Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. 4 Department of Transfusion Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, Japan.…”

Section: Declarations Ethics Approval and Consent To Participatementioning

confidence: 99%

“…Multi-gene panel testing of cancer by using next-generation sequencing (NGS) is now widespread, leading to proposals for optimal treatment of individual cancer patients in the clinical practice of oncology [ 1 , 2 ]. Therapeutic approaches targeting driver gene abnormalities have been separately developed for each cancer type [ 3 ], but the basket trials, which examine whether a molecular targeted agent works for various types of cancers with the same driver gene abnormalities, are increasing [ 4 ]. Variants of the HER2 gene, which encodes the human epidermal growth factor receptor 2 (HER2) protein, are one of the most promising therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Anti-cancer effect of afatinib, dual inhibitor of HER2 and EGFR, on novel mutation HER2 E401G in models of patient-derived cancer

et al. 2023

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Background Precision medicine with gene panel testing based on next-generation sequencing for patients with cancer is being used increasingly in clinical practice. HER2, which encodes the human epidermal growth factor receptor 2 (HER2), is a potentially important driver gene. However, therapeutic strategies aimed at mutations in the HER2 extracellular domain have not been clarified. We therefore investigated the effect of EGFR co-targeted therapy with HER2 on patient-derived cancer models with the HER2 extracellular domain mutation E401G, based on our previous findings that this mutation has an epidermal growth factor receptor (EGFR)-mediated activation mechanism. Methods We generated a xenograft (PDX) and a cancer tissue-originated spheroid (CTOS) from a patient’s cancer containing an amplified HER2 E401G mutation. With these platforms, we compared the efficacy of afatinib, a tyrosine kinase inhibitor having anti-HER2 and anti-EGFR activity, with two other therapeutic options: lapatinib, which has similar properties but weaker EGFR inhibition, and trastuzumab plus pertuzumab, for which evidence exists of treatment efficacy against cancers with wild-type HER2 amplification. Similar experiments were also performed with H2170, a cell line with wild-type HER2 amplification, to contrast the characteristics of these drug’s efficacies against HER2 E401G. Results We confirmed that PDX and CTOS retained morphological and immunohistochemical characteristics and HER2 gene profiles of the original tumor. In both PDX and CTOS, afatinib reduced tumor size more than lapatinib or trastuzumab plus pertuzumab. In addition, afatinib treatment resulted in a statistically significant reduction in HER2 copy number at the end of treatment. On the other hand, in H2170 xenografts with wild-type HER2 amplification, trastuzumab plus pertuzumab was most effective. Conclusions Afatinib, a dual inhibitor of HER2 and EGFR, showed a promising effect on cancers with amplified HER2 E401G, which have an EGFR-mediated activation mechanism. Analysis of the activation mechanisms of mutations and development of therapeutic strategies based on those mechanisms are critical in precision medicine for cancer patients.

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Genomic testing among patients with newly diagnosed advanced non-small cell lung cancer in the United States: A contemporary clinical practice patterns study

Cited by 21 publications

References 38 publications

Optimizing molecular testing of lung cancer needle biopsy specimens: potential solutions from an interdisciplinary qualitative study

Optimizing molecular testing of lung cancer needle biopsy specimens: potential solutions from an interdisciplinary qualitative study

Targeted therapy for lung cancer: Beyond EGFR and ALK

Anti-cancer effect of afatinib, dual inhibitor of HER2 and EGFR, on novel mutation HER2 E401G in models of patient-derived cancer

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