Molecular testing of metastatic<scp>non‐small</scp>cell lung cancer in the<scp>Asia‐Pacific</scp>region

Ck, Liam; Andarini, Sita; Liam, Yong-Sheng; Lam, David Chi‐Leung; Lee, Pyng

doi:10.1111/resp.13833

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…Specifically, EGFR L858R and in-frame exon 19 deletions account for 50 and 40% of EGFR mutations, respectively, and are sensitizing mutations as tumors harboring these mutations are sensitive to EGFR TKIs (23). Molecular testing for alterations in multiple genes such as EGFR, ALK, ROS1, RET, BRAF, ERRB2, MET exon 14, and NTRK1/2/3 have progressively entered the standard of care over the last 10 years (24). Here, we aim to demonstrate the clinical utility of an ultrasensitive, amplicon-based NGS tool for plasma cfDNA testing alongside standard tissue testing in patients suspected to have lung cancer, to widen the scope of eligibility for treatment and reduce waiting time for molecular test results.…”

Section: Introductionmentioning

confidence: 99%

Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer

Choudhury¹,

Tan²,

Shi

et al. 2022

Front. Med.

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BackgroundTissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and limited by heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging.MethodsPatients with suspected lung cancer (n = 71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 h of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples (tissue EGFR testing), where available. Concordance of clinically actionable mutations between methods and sample types was assessed.ResultsFor confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF, and MET. The overall sensitivity of sensitizing EGFR mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n = 37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a 1.9-fold increase in clinically relevant findings. The average turnaround time of plasma NGS was shorter than standard tissue testing (10 vs. 29.9 days, p < 0.05).ConclusionsIn the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with a shorter time to results. This study outlines the clinical utility of complementary plasma mutation profiling in the routine management of lung cancer patients.

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Section: Introductionmentioning

confidence: 99%

Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer

Choudhury¹,

Tan²,

Shi

et al. 2022

Front. Med.

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“…However, recent advances in immune therapy and targeted therapy have radically improved the treatment paradigm of NSCLC over the past decade [ 2 ]. Molecular profiling of lung cancer samples for activated oncogenes, including epidermal growth factor receptor ( EGFR ), anaplastic lymphoma kinase ( ALK ) and c–ros oncogene 1 ( ROS1 ), is considered as standard-of care to select the most appropriate up-front treatment [ 3 ]. However, the identification of new therapeutic targets remains a high priority.…”

Section: Introductionmentioning

confidence: 99%

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Zhu

Lu²,

Lü

2022

Cancers

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Non-small cell lung cancer (NSCLC) is increasingly being treated with targeted therapies. Savolitinib (Orpathys®) is highly selective mesenchymal epithelial transition (MET)–tyrosine kinase inhibitor (TKI), which is conditionally approved in China for advanced NSCLC with MET exon 14 skipping mutations (METex14). This article summarizes the clinical development of savolitinib, as a monotherapy in NSCLC with METex14 mutation and in combination with epidermal growth factor receptor (EGFR) inhibitor in post EGFR–TKI resistance NSCLC due to MET-based acquired resistance. Preclinical models demonstrated anti-tumor activities in MET-driven cancer cell line and xenograft tumor models. The Phase Ia/Ib study established an optimized, recommended phase II dose in Chinese NSCLC patients, while TATTON study of savolitinib plus osimertinib in patients with EGFR mutant, MET-amplified and TKI-progressed NSCLC showed beneficial efficacy with acceptable safety profile. In a pivotal phase II study, Chinese patients with pulmonary sarcomatoid carcinoma, brain metastasis and other NSCLC subtype positive for METex14 mutation showed notable responses and acceptable safety profile with savolitinib. Currently, results from ongoing clinical trials are eagerly anticipated to confirm the efficacious and safety benefits of savolitinib as monotherapy and in combination with EGFR–TKI in acquired resistance setting in advanced NSCLC and its subtypes with MET alterations.

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“…Specifically, EGFR L858R and in-frame exon 19 deletions, account for 50% and 40% of EGFR mutations, respectively, and are sensitizing mutations as tumors harboring these mutations are sensitive to EGFR tyrosine kinase inhibitors (TKI) 23 . Molecular testing for alterations in multiple genes such as EGFR, ALK, ROS1, RET, BRAF, ERRB2, MET exon 14 and NTRK1/2/3 have progressively entered the standard of care over the last 10 years 24 .…”

Section: Introductionmentioning

confidence: 99%

Complementing Tissue Testing with Plasma mutation Profiling Improves Therapeutic Decision Making for Lung Cancer Patients

Choudhury¹,

Tan²,

Shi

et al. 2021

Preprint

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Background: Tissue biopsy is an integral part of the diagnostic approach to lung cancer. It is however invasive and associated with limitations of tissue heterogeneity. Liquid biopsies may complement tissue testing by providing additional molecular information and may be particularly helpful in patients from whom obtaining sufficient tissue for genomic profiling is challenging. Methods: Patients with suspected lung cancer (n=71) were prospectively recruited. Blood and diagnostic tissue samples were collected within 48 hrs of each other. Plasma cell-free DNA (cfDNA) testing was done using an ultrasensitive amplicon-based next-generation sequencing (NGS) panel (plasma NGS testing). For cases diagnosed as non-small cell lung carcinoma (NSCLC) via histology or cytology, targeted testing for epidermal growth factor receptor (EGFR) mutations was performed using tissue biopsy samples, where available (tissue EGFR testing). Concordance of clinically actionable mutations between methods and sample types were assessed. Results: For confirmed NSCLC cases (n = 54), tissue EGFR test results were available only for 70.3% (38/54) due to sample inadequacies, compared to blood samples for 98.1% (53/54) cases. Tissue EGFR testing identified sensitizing EGFR (L858R or exon 19 deletion) mutation in 31.6% (12/38) of cases. Plasma NGS identified clinically actionable mutations in 37.7% (20/53) of cases, including EGFR mutations in two cases with no tissue EGFR results, and mutations in KRAS, BRAF and MET. Overall sensitivity of EGFR sensitizing mutation detection by plasma NGS was 75% (9/12), and specificity was 100% (25/25) in patients tested in both tissue EGFR and plasma NGS (n=37). In this cohort of patients, tissue EGFR testing alone informed clinical decisions in 22.2% (12/54) of cases. Adding plasma NGS to tissue EGFR testing increased the detection rate of actionable mutations to 42.6% (23/54), representing a near doubling (1.9-fold increase) of clinically relevant findings. The average turnaround time (TAT) of plasma NGS was shorter than standard tissue testing (10 days vs. 29.9 days, p-value <0.05). Conclusions: In the first-line setting, plasma NGS was highly concordant with tissue EGFR testing. Plasma NGS increases the detection of actionable findings with shorter time to results. This study outlines the clinical utility of a complementary plasma mutation profiling in the routine management of lung cancer patients.

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Molecular testing of metastaticnon‐smallcell lung cancer in theAsia‐Pacificregion

Cited by 4 publications

References 6 publications

Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer

Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With Lung Cancer

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Complementing Tissue Testing with Plasma mutation Profiling Improves Therapeutic Decision Making for Lung Cancer Patients

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