EGFR exon 19 deletion switch and development of p.L792Q mutation as a new resistance mechanism to osimertinib: a case report and literature review

Pisapia, Pasquale; Rocco, Danilo; Pepe, Francesco; Luca, Caterina De; Battiloro, Ciro; Smeraglio, Riccardo; Cieri, Miriam; Bellevicine, Claudio; Troncone, Giancarlo; Malapelle, Umberto

doi:10.21037/tcr.2018.09.13

Cited by 14 publications

(13 citation statements)

References 23 publications

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“…In a cohort study conducted by Yang et al (2), L792X and L718X mutations were identified in 10.8% (10/93) and 9.7% (9/ 93) of osimertinib-resistant NSCLC cases, but were higher than those in 28.9% (11/38) and 18.4% (7/38) of T790M-ratained NSCLC cases, respectively. In addition, most L792-mutated cases have a concomitant cis T790M mutation, which is consistent with previous studies (4,5,13). In our study, two of the three cases harboring L792X mutations retained the T790M mutation and were both in cis with T790M; however, the other three cases harboring L718X mutations were absent from T790M.…”

Section: Discussionsupporting

confidence: 92%

Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

Gao

Wang

2021

Front. Oncol.

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The acquired EGFR C797X mutation has been identified as the most notable resistance to osimertinib, and novel secondary mutations of EGFR L718 and L792 residues have also been demonstrated to confer osimertinib resistance, making the choice of medication after osimertinib treatment a quandary. Dacomitinib has been reported to have potential impact on patients acquiring rare compound mutations after osimertinib resistance; however, little evidence is available to date. In five lung adenocarcinoma patients resistant to later-line osimertinib, recurrent mutations at EGFR L792 and/or L718 were identified using targeted next-generation sequencing of tissue or cell-free DNA from plasma or pleural effusion. Dacomitinib was initiated after osimertinib resistance; however, all patients progressed within 2 months. Molecular structural simulation revealed that L792H + T790M and L718Q mutations could interfere with the binding of dacomitinib to EGFR and potentially cause primary drug resistance. Our case series study, to our knowledge, is the first to report the clinical efficacy of dacomitinib in patients harboring rare complex mutations after later-line osimertinib resistance.

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Section: Discussionsupporting

confidence: 92%

Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

Gao

Wang

2021

Front. Oncol.

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“…As a general rule, in our clinical practice, liquid biopsy is performed upon oncologist request. Patients are received directly in our Institution where a nurse, who is a permanent member of our molecular laboratory staff, collect in EDTA Vacutainer tubes (BD, Plymount, UK) ten mL of peripheral blood, as previously described (27,29,30). By this in-house approach, samples are immediately processed in order to avoid the risk of circulating tumor DNA (ctDNA) degradation.…”

Section: Ngs Analysismentioning

confidence: 99%

“…In our Institution we routinely adopt NGS to assess NSCLC biomarkers; to this end, we designed a customized NGS panel, that makes cost-effective the batching of different tumor samples. In fact, this panel, termed SiRe ® , is meant to provide a unique workflow of samples for different specimen types (tissue and liquid biopsies) (27)(28)(29)(30). Thus, whenever tissue is not adequate or available for NGS testing, which is a common occurrence for advanced stage NSCLC patients, SiRe ® NGS plasma based analysis is a viable option to assess EGFR mutational status (31).…”

mentioning

confidence: 99%

KRAS mutations testing in non-small cell lung cancer: the role of Liquid biopsy in the basal setting

Nacchio¹,

Sgariglia²,

Gristina³

et al. 2020

J Thorac Dis

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IntroductionLung cancer is the most frequent cause of cancer death, worldwide (1). In the last years, several clinical trials have defined the pivotal role of the molecular assessment of different biomarkers, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), v-Raf murine sarcoma viral oncogene homolog B (BRAF), and programmed death-ligand 1 (PD-L1), in order to administrate either tyrosine kinase inhibitors (TKIs) or immune-checkpoint inhibitors to improve survival and quality of life of advanced stage non-small cell lung cancer (NSCLC) patients (2-14).

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“…Targeted therapy for epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) developed quickly (1)(2)(3)(4)(5). EGFR exon 19 deletion (19del) was about 44% in EGFR mutations, and the most frequent subtype was delE756_A750, followed by delL747_P753insS, delL747_A750insP or delL747_T751 (6,7).…”

Section: Introductionmentioning

confidence: 99%

The impact of EGFR exon 19 deletion subtypes on clinical outcomes in non-small cell lung cancer

Zhao¹,

Jiang²,

Li³

et al. 2020

Transl Lung Cancer Res

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Background:The study investigated the resistant pattern and clinical outcomes of epidermal growth factor receptor (EGFR) exon 19 deletion (19del) subtypes to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC).Methods: Two hundred eight treatment naive NSCLC patients detected as EGFR 19del using amplification-refractory mutation system (ARMS) were included. DNA sequencing was used to detect the subtypes. Clinicopathological features as well as patients' outcomes treated with first-line EGFR-TKIs were analyzed.Results: Thirteen EGFR 19del subtypes were confirmed in 181 samples (87.0%). Among these, delE746_ A750 was the most frequent subtype (130/181, 71.8%). delE746_A750 and deletions starting from E746 were frequently found in female (P=0.003 and P=0.013, respectively) and never smokers (P=0.002 and P=0.014, respectively) than non-delE746_A750 and deletions starting from L747 patients, respectively. T790M was more frequently occurred in delE746_A750 than non-delE746_A750 (P=0.001) and deletions starting from E746 than L747 patients (P=0.006) after first-line EGFR-TKIs resistance. Patients harboring deletions starting from L747 with insertions had significantly shorter progression-free survival (PFS) than deletions starting from L747 without insertion (8.3 vs. 15.0 m, P=0.017), or all other patients (8.3 vs. 12.6 m, P=0.027). Different 19del subtypes with T790M mutation had similar PFS when treated with osimertinib (P=0.102). Conclusions: Patients with EGFR 19del subtypes had different clinicopathological features, and resistant pattern when treated with first-line TKIs. Patients harboring deletions starting from L747 with insertions had inferior outcomes than other subtypes.

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EGFR exon 19 deletion switch and development of p.L792Q mutation as a new resistance mechanism to osimertinib: a case report and literature review

Cited by 14 publications

References 23 publications

Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

KRAS mutations testing in non-small cell lung cancer: the role of Liquid biopsy in the basal setting

The impact of EGFR exon 19 deletion subtypes on clinical outcomes in non-small cell lung cancer

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