&lt;p&gt;Durable Response to Osimertinib in a Chinese Patient with Metastatic Lung Adenocarcinoma Harboring a Rare EGFR L858R/D761Y Compound Mutation&lt;/p&gt;

Zhu, Yeping; Tang, Jianning; Li, Xin; Tian, Qing; Yang, Wei

doi:10.2147/ott.s268593

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…A 62-year-old non-smoking woman with advanced lung adenocarcinoma who responded with stable disease (SD) to sequential treatments with Icotinib and Osimertinib, the PFS with Osimertinib treatment is much longer than that with Icotinib (19 months vs 8.2 months) and the OS is more than 3 years. [13] Besides, an in vitro study has showed that despite displaying resistance to first-generation reversible EGFR-TKIs, L858R/D761Y mutant cells were sensitive to irreversible inhibitors, especially the third-generation EGFR-TKIs. [14] However, in this case, we reported a lung adenocarcinoma patient carrying D761Y mutation present before EGFR-TKI treatment.…”

Section: Discussionmentioning

confidence: 99%

De Novo mutation in Epidermal growth factor receptor (EGFR)-D761Y responding to third generation tyrosine kinase inhibitor Osimertinib: A case report

Ding

Dong

et al. 2022

Medicine

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Introduction: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) mutations are the most common accurate gene targets. However, the lack of case reports or cohort studies on the exceptionally rare mutations limit the acquisition of deeper insights. Patient concerns: A 76-year-old female nonsmoker presented to our hospital with a one-week disease history of cough accompanied by shortness of breath. Diagnosis: Contrast-enhanced CT scan showed right pleural effusion with scattered inflammation and consolidation in the right upper lung. Tumor marker display showed obvious increased. Histopathology of the pulmonary mass combined with Immunohistochemical staining indicated lung adenocarcinoma. Contrast-enhanced magnetic resonance imaging suggested brain metastases. ECT scan showed bone metastasis. The patient was thus diagnosed as right lung adenocarcinoma of stage IV (cT3N3M1c). Next generation sequencing was performed to profile the mutation status of known oncogenic driver mutations, and only EGFR-D761Y in exon 19 (allelic frequency, AF: 0.53%) mutation was found. Interventions: The patient was accordingly treated with the third generation EGFR-Epidermal growth factor receptor tyrosine kinase inhibitor (TKI) Osimertinib (80 mg, qd). Accompanied with whole brain radiotherapy (DT3000c Gy/10f) for brain metastases, technetium methylene diphosphonate injection was performed for bone metastases. Outcomes: The efficacy of the first-line Osimertinib treatment for 1 month was assessed as PR per RECIST version 1.1. The NSCLC patient harboring EGFR-D761Y mutation detected prior to the EGFR L858R mutation was benefited from the third-generation EGFR-TKI Osimertinib and had a worse prognosis than with other EGFR mutations according to data from previous case reports. Conclusions: This case reported a NSCLC patient with de novo mutation of EGFR-D761Y responding to third generation TKI Osimertinib.

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Section: Discussionmentioning

confidence: 99%

De Novo mutation in Epidermal growth factor receptor (EGFR)-D761Y responding to third generation tyrosine kinase inhibitor Osimertinib: A case report

Ding

Dong

et al. 2022

Medicine

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“…Another case reported a patient carrying an uncommon L858R/D761Y compound mutation in EGFR. Osimertinib treatment lead to a PFS of 19 months and OS of more than 3 years ( 24 ).…”

Section: The Efficacy Of Osimertinib In Nsclc Patients With Uncommon ...mentioning

confidence: 99%

Osimertinib-Centered Therapy Against Uncommon Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer- A Mini Review

Song

Yang

2022

Front. Oncol.

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Osimertinib is a third-generation, irreversible mutant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Osimertinib is currently the first line drug recommended by National Comprehensive Cancer Network (NCCN) guidelines against lung cancer harboring the EGFR TKI-sensitive mutation and acquired EGFR T790M resistance mutation. Osimertinib demonstrated some efficacy in clinical trials and case reports in patients bearing certain uncommon EGFR mutations, but it is not active in patients with other mutations such as C797S. This mini-review presents the mechanisms underlying the variations in patient responses, discusses the use of osimertinib against non-small-cell lung carcinomas with uncommon EGFR mutations, and addresses the future prospects of osimertinib-centered therapy.

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Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)

et al. 2022

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According to global cancer data, lung cancer was the leading cause of cancer-related death in 2020. With the diversification of treatment strategies, the survival outcomes of patients with advanced lung cancer have improved significantly, but the 5-year overall survival rate remains <20%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment for lung adenocarcinoma patients with EGFR-sensitive mutations; however, acquired drug resistance is inevitable. Osimertinib (a third-generation EGFR inhibitor) is the most commonly used drug for cancers with a secondary T790M mutation. Unfortunately, acquired drug resistance against third-generation drugs still emerges. The C797s mutation is the primary acquired resistance mechanism against Osimertinib. Research on fourth-generation EGFR-TKI drugs with a C797s mutation is currently at various experimental stages, and no drug has been approved for clinical use. In addition to the resistance mechanisms described above, HER2 amplification, MET amplification, PIK3A mutation, KRAS mutation, BRAF mutation, transformation to small cell lung cancer, transformation to lung squamous cell carcinoma, and EMT have been reported as mechanisms of acquired drug resistance to first-, second-and third-generation EGFR-TKIs. These mechanisms are noted in a relatively high proportion of tumors, but treatment options are limited. In recent years, immunotherapy has made progress in the treatment of several cancers, including advanced EGFR-mutated non-small cell lung cancer (NSCLC). Due to the relatively high frequency of EGFR mutation in patients with lung adenocarcinoma in China, an increased number of patients develop EGFR-TKI resistance, and subsequent treatment options are critical. This article reviews the mechanisms of drug resistance to different EGFR-TKIs and treatment progression, providing ideas for the follow-up treatment for EGFR-resistant patients.

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<p>Durable Response to Osimertinib in a Chinese Patient with Metastatic Lung Adenocarcinoma Harboring a Rare EGFR L858R/D761Y Compound Mutation</p>

Cited by 3 publications

References 12 publications

De Novo mutation in Epidermal growth factor receptor (EGFR)-D761Y responding to third generation tyrosine kinase inhibitor Osimertinib: A case report

De Novo mutation in Epidermal growth factor receptor (EGFR)-D761Y responding to third generation tyrosine kinase inhibitor Osimertinib: A case report

Osimertinib-Centered Therapy Against Uncommon Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer- A Mini Review

Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)

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