Efficacy of osimertinib in a patient with non‑small cell lung cancer harboring epithelial growth factor receptor exon 19 deletion/T790M mutation, with poor performance status

Nishii, Yoichi; Hasegawa, Osamu; Ito, Kentaro; Watanabe, Fumiaki; Kobayashi, Tetsu; D’Alessandro-Gabazza, Corina N.; Toda, Masaaki; Taguchi, Osamu; Yamamoto, Nobuyuki; Gabazza, Esteban C.

doi:10.3892/mco.2017.1522

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…Several researches have clarified that NSCLC patients harboring EGFR exon 19 deletion or exon 21 L858R can benefit from icotinib and osimertinib. 26,27 In this study, 38.82% of MM patients bearing EGFR mutations in the 18-21 exon region, among which exon 19 deletion and L858R accounted for 62.5% of all EGFR mutations. The lung adenocarcinoma patients harboring sensitive EGFR mutations benefit from EGFR-TKI drugs.…”

Section: Discussionmentioning

confidence: 58%

The Presence of Genomic Instability in Cerebrospinal Fluid in Patients with Meningeal Metastasis

Wang¹,

Zhang²,

Chen³

et al. 2021

CMAR

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This study aimed to explore the genomic instability in cerebrospinal fluid (CSF) in patients with meningeal metastasis (MM). Material and Methods: We collected the blood and CSF samples of 15 MM patients and one brain parenchymal metastasis (BPM) patient. A panel of 543 cancer-related genes was conducted to analyze the status of genomic instability in CSF and plasma cellfree DNA (cfDNA) of all patients. Subsequently, nine patients underwent low-depth whole-genome sequencing (WGS) analysis to verify the existence of genomic instability, followed by genomic scoring by the application of aneuploidy scores. Diagnosis-specific graded prognostic assessment (DS-GPA) score was utilized to assess the clinical status of MM patients. Results: There was significant difference in gene mutation between CSF cfDNA and plasma cfDNA in MM patients. Among them, 12 MM patients developed genomic instability in their CSF cfDNA, while the remaining 3 had stable genetic profile. Besides, BPM patients showed genomic stability in his CSF and paraffin-embedded tissue sections. No genomic instability was noticed in plasma cfDNA of all patients. Sensitive mutations on EGFR, ERBB2, ALK and KRAS genes and increased gene copy numbers of MET and ERBB2 were detected in 10 MM patients with genomic instability, as well as the EGFR gene mutation in one MM case with genomic stability. Additionally, MM patients with genomic instability had lower overall survival and higher aneuploidy scores and tumor mutation burden compared with those with genomic stability. Moreover, MM patients with higher DS-GPA scores benefited from better survival. Conclusion: Genomic instability existed in the CSF cfDNA rather than plasma cfDNA of MM patients, which might be the underlying cause of the differences in MM.

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Section: Discussionmentioning

confidence: 58%

The Presence of Genomic Instability in Cerebrospinal Fluid in Patients with Meningeal Metastasis

Wang¹,

Zhang²,

Chen³

et al. 2021

CMAR

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“…Takashi et al [ 9 ] demonstrated that osimertinib regressed bone tumors in mice with EGFR-mutant lung adenocarcinoma and bone metastases, resulting in improved survival and bone remodeling in the mice. Similarly, Ying et al [ 10 ] and Yoichi et al [ 11 ] reported that patients treated with osimertinib experienced regression of bone metastases and longer-term survival rates. These findings align with those of our study, in which patients with bone metastases from lung adenocarcinoma with EGFR 19del mutation had longer-term control of both primary tumors and bone metastases, with PFS of 18 and 22 months and even longer OS after targeted therapy with osimertinib, following different treatments such as chemotherapy, radiotherapy, and surgery.…”

Section: Discussionmentioning

confidence: 97%

Efficacy of 3rd generation TKI in patients with EGFR mutation lung adenocarcinoma with bone metastases: A review of 3 case reports and literature

Guo,

Feng,

et al. 2023

Medicine

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Rationale: With the advancement of targeted therapies, epidermal growth factor receptor tyrosine kinase inhibitors have become the preferred initial treatment for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is effective against exon 19 and 21 mutations as well as the T790M mutation. It has been approved by both the food and drug administration and European Medicines Agency for the treatment of non-small cell lung cancer patients with locally advanced or metastatic EGFR-mutated tumors, including those who have acquired T790M mutations. Patient concerns: To evaluate the effectiveness of osimertinib in treating patients with EGFR-mutated advanced lung adenocarcinoma and bone metastases, we present the treatment outcomes of 3 patients with EGFR 19 deletion-mutated advanced lung adenocarcinoma and bone metastases who received osimertinib treatment in recent years. All 3 cases involved elderly female patients, aged 62, 62, and 54, respectively. Diagnoses: All 3 cases exhibited a diagnosis of pulmonary adenocarcinoma accompanied by osseous metastases, with genetic testing revealing the presence of an EGFR 19del mutation. Interventions: In the first case, following 17 months of gefitinib therapy, disease progression prompted a switch to osimertinib treatment. In the second case, bone metastases were detected after 20 months of pemetrexed-carboplatin chemotherapy, leading to a transition to osimertinib therapy. In the third case, after 11 months of erlotinib treatment, bone metastases were identified. Subsequent interventions, including radiation therapy, pemetrexed-carboplatin chemotherapy, pemetrexed-bevacizumab maintenance therapy, and docetaxel chemotherapy, failed to arrest the progression of bone metastases. As a result, a combination of osimertinib and anlotinib targeted therapy was administered. Outcomes: All 3 patients experienced relatively good and favorable survival outcomes, with a progression-free survival of 22.7 months, 12 months, and 17.7 months, respectively. Lessons: These cases suggest that osimertinib is a promising treatment option for patients with EGFR 19 deletion-mutated lung adenocarcinoma and bone metastases, although further clinical studies are needed to confirm its efficacy.

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“…This suggests that patients with advanced EGFR m+ NSCLC despite having poor ECOG performance status, do derive OS benefits when treated with EGFR TKIs as previously reported. 27 , 28 …”

Section: Discussionmentioning

confidence: 99%

Outcomes of Patients with EGFR-Mutant Advanced NSCLC in a Developing Country in Southeast Asia

How¹,

Liam²,

Abidin³

et al. 2022

CMAR

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Background Although first- and second-generation EGFR TKIs are considered first-line treatment in EGFRm+ NSCLC, most patients develop resistance and progress, commonly, EGFR T790M mutation. The third-generation EGFR-TKI has demonstrated efficacy in patients with progressive disease harboring the T790M mutation and in the first-line setting, bypassing this mode of resistance. The primary objectives of this study are to describe the proportion of EGFR m+ NSCLC patients treated with first-, second- and third-generation EGFR TKIs, and cytotoxic chemotherapy in the first-line setting, and the time on treatment for each category. Secondary objectives are to determine the dropout rate, the rates for T790M mutation testing at disease progression and the type of subsequent treatment. Methods This multicenter retrospective study utilized data from the Malaysian Lung Cancer Registry that actively registers all lung cancer patients ≥18 years, with primary lung cancer confirmed histologically or cytologically. All patients diagnosed with advanced stages (ie stages IIIB, IIIC and IV) EGFR m+ NSCLC from 1st of January 2015 to 31st December 2019 were included. Results Of 406 patients with EGFR m+ NCSLC, 351 were treated. Types of first-line treatment were as follows: EGFR-TKIs (first generation – 54.1%, second generation – 25.6% and third-generation – 12.5%) and chemotherapy (7.7%). The median time of treatment for each generation of EGFR-TKI was 12 months, 12 months and 24 months, and 2 months for chemotherapy. The dropout rate was 28.7% (n = 101). Nearly half (49.4%) of patients who were on first- or second-generation EGFR-TKI had further genetic testing via liquid or tissue biopsies upon disease progression. About 24.9% of those who developed disease progression after first- or second-generation EGFR TKI were started on a third-generation EGFR TKI. Conclusion In the real-world, the management of EGFR m+ advanced NSCLC patients in an Asian cost-restrictive setting may adversely affect the choice of first-line therapy, time on each line of treatment and subsequently the overall survival of patients.

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Efficacy of osimertinib in a patient with non‑small cell lung cancer harboring epithelial growth factor receptor exon 19 deletion/T790M mutation, with poor performance status

Cited by 8 publications

References 12 publications

The Presence of Genomic Instability in Cerebrospinal Fluid in Patients with Meningeal Metastasis

The Presence of Genomic Instability in Cerebrospinal Fluid in Patients with Meningeal Metastasis

Efficacy of 3rd generation TKI in patients with EGFR mutation lung adenocarcinoma with bone metastases: A review of 3 case reports and literature

Outcomes of Patients with EGFR-Mutant Advanced NSCLC in a Developing Country in Southeast Asia

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