EGFR mutation analysis for prospective patient selection in AURA3 phase III trial of osimertinib versus platinum-pemetrexed in patients with EGFR T790M-positive advanced non-small-cell lung cancer

John, Thomas; Akamatsu, Hiroaki; Delmonte, Angelo; Su, Wu Chou; Lee, Jong Seok; Chang, Gee Chen; Huang, Xiangning; Jenkins, Suzanne; Wu, Yi Long

doi:10.1016/j.lungcan.2018.10.027

Cited by 38 publications

(33 citation statements)

References 23 publications

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“…As a component of liquid biopsy, ctDNA has the most potential clinical application value due to its non-invasive, real-time and highly specific genomic result. 26,27 Currently, the clinical utility of ctDNA is only approved in metastatic non-small-cell lung cancer (NSCLC) by FDA as a companion diagnostic, 28,29 while studies on many other cancers have also shown good prospects. [30][31][32][33][34][35][36] The fact that even little variability in process and analysis will result in completely different results restrains the further clinical utility of ctDNA.…”

Section: Discussionmentioning

confidence: 99%

Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients

et al. 2020

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BACKGROUND: About 25-37% of resectable pancreatic ductal adenocarcinoma (PDAC) had a great chance of early recurrence after radical resection, which is mainly due to preoperative micrometastasis. We herein demonstrated the profiles of ctDNA in resectable PDAC and use of ctDNA to identify patients with potential micrometastasis. METHODS: A total of 113 and 44 resectable PDACs were enrolled in discovery and validation cohorts, separately. A panel containing 50 genes was used to screen ctDNA by an NGS-based assessment with high specificity. RESULTS: In the discovery cohort, the overall detection rate was 38.05% (43/113). Among positive ctDNA, KRAS mutation had the highest detection rate (23.01%, 26/113), while the others were <5%. Survival analysis showed that plasma KRAS mutations, especially KRAS G12D mutation, had significant association with OS and RFS of resectable PDAC. Plasma KRAS G12D mutation showed a strong correlation with early distant metastasis. In the validation cohort, survival analysis showed similar association between plasma KRAS G12D mutation and poor outcomes. CONCLUSIONS: This study demonstrated that plasma KRAS mutations, especially KRAS G12D mutation, served as a useful predictive biomarker for prognosis of resectable PDAC. More importantly, due to high correlation with micrometastasis, preoperative detection of plasma KRAS G12D mutation helps in optimising surgical selection of resectable PDAC.

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Section: Discussionmentioning

confidence: 99%

Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients

et al. 2020

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“…The peptide nucleic acidlocked nucleic acid (PNA-LNA) PCR clamp method [11] was used to detect the EGFR mutation, using tissue biopsy specimens during the initial diagnosis of non-small non-squamous-cell lung cancer. After EGFR-mutated lung cancer acquired clinical resistance to EGFR-TKIs, the cobas® EGFR Mutation Test (Version 2; Roche Molecular Systems) [10] was repeatedly performed to detect the T790M mutation status through tissue or liquid biopsy. Clinical resistance was defined as an increase in monitoring of tumor markers, disease progression through radiological imaging, or clinical disease progression.…”

Section: Patientsmentioning

confidence: 99%

“…Among patients not harboring the T790M substitution, tissue or liquid rebiopsies were repeated numerous times until the T790M substitution was detected. Cobas® version 2 is a single plexus real-time PCR procedure to detect EGFR mutations, which potentially uses unstained 5-μm-thick sections obtained from a formalinfixed paraffin-embed (FFPE) block and mounted on slides or whole blood samples, as previously reported [10]. Mutations were analyzed at the central laboratory of LSI Medience Corporation (Tokyo, Japan).…”

Section: Rebiopsy and Genetic Analysismentioning

confidence: 99%

Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations

Takeda

Naka

Yamaguchi

et al. 2020

Preprint

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Background: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than first-generation EGFR-TKIs used for first-line treatment, their efficacy for long-term patient survival remains unclear even upon administration of a complete sequence of EGFR-TKI therapy, and limited information is available regrading genetic diagnostic approaches after EGFR-TKI naïve treatment. This study aimed to investigate the characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs and the advantages of rebiopsy and liquid biopsy among these patients.Methods: The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs except for osimertinib, single plexus COBAS version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy. Results: From April 2016 through May 2019, 113 patients harbored EGFR mutations. Sixty patients were treated with EGFR-TKIs, among which 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, displayed a new lesion, and were administered gefitinib as first-line therapy, patients harboring an EGFR mutation were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with co-existing original mutations, brain metastases, tumor enlargement by ≥ 12 mm, or metastases at rare sites. Conclusion: Repeated biopsy can help maximize the detection rate of the T790M substitution. Furthermore, the advantages of repeated tissue or liquid biopsy should be considered among patients with positive T790M factors, and these biopsies can be repeated numerous times.

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“…The peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method [11] was used to detect the EGFR mutation, using tissue biopsy specimens during the initial diagnosis of non-small non-squamous-cell lung cancer. After EGFRmutated lung cancer acquired clinical resistance to EGFR-TKIs, the cobas® EGFR Mutation Test (Version 2; Roche Molecular Systems) [10] was repeatedly performed to detect T790M mutation status through tissue or liquid biopsy. Clinical resistance was de ned as an increase in monitoring of tumor markers, disease progression through radiological imaging, or clinical disease progression.…”

Section: Patientsmentioning

confidence: 99%

“…Among patients not harboring the T790M substitution, tissue or liquid rebiopsies were repeated numerous times until the T790M substitution was detected. Cobas® version 2 is a single plexus real-time PCR procedure to detect EGFR mutations, which potentially uses unstained 5-μm-thick sections obtained from a formalin-xed para n-embed block and mounted on slides or whole blood samples, as previously reported [10]. Mutations were analyzed at the central laboratory of LSI Medience Corporation (Tokyo, Japan).…”

Section: Rebiopsy and Genetic Analysismentioning

confidence: 99%

Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations

Takeda

Naka

Yamaguchi

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Osimertinib, a third - generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as a second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy, and limited information is available regarding genetic diagnostic approaches after EGFR-TKI naïve treatment. This study investigated the characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistance to EGFR-TKIs and the advantages of rebiopsy and liquid biopsy for these patients. Methods: The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy. Results: From April 2016 through May 2019, 113 patients were determined to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among which 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had new lesions, and were administered gefitinib as first-line therapy, patients harboring an EGFR mutation were suspected of harboring the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with co-existing original mutations, brain metastases, tumor enlargement by ≥ 12 mm, or metastases at minor sites. Conclusion: Repeated biopsy can help maximize the detection rate of the T790M substitution. Furthermore, the advantages of repeated tissue or liquid biopsy should be considered among patients with positive T790M factors , and these biopsies can be repeated numerous times .

show abstract

EGFR mutation analysis for prospective patient selection in AURA3 phase III trial of osimertinib versus platinum-pemetrexed in patients with EGFR T790M-positive advanced non-small-cell lung cancer

Cited by 38 publications

References 23 publications

Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients

Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients

Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations

Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations

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