Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

Sobue, Gen; Tanaka, Ichidai; Morise, Masahiro; Koyama, Junji; Kodama, Yuta; Matsui, Akira; Miyazawa, Akiyoshi; Hase, Takashi; Hibino, Yoshitaka; Yokoyama, Toshihiko; Kimura, Tomoki; Yoshida, Norio; Sato, Mitsuo; Hashimoto, Naozumi

doi:10.1186/s12885-022-09741-8

Cited by 25 publications

(30 citation statements)

References 37 publications

(40 reference statements)

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“…In a subgroup analysis of 118 patients with metastatic NSCLC disease in the brain, this study reported a longer PFS with Osimertinib compared to 1st gen TKIs erlotinib/gefitinib and 2nd gen TKI afatinib (16.3 vs. 7.9 vs. 8.3 months respectively). An improvement in OS was also noted to be trending towards significance with the use of Osimertinib compared to erlotinib/gefitinib (not reached vs. 20.9 months, p = 0.0725) [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

First- versus Third-Generation EGFR Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases

Tatineni

O’Shea

Ozair

et al. 2023

Cancers

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Introduction: Up to 50% of non-small cell lung cancer (NSCLC) harbor EGFR alterations, the most common etiology behind brain metastases (BMs). First-generation EGFR-directed tyrosine kinase inhibitors (EGFR-TKI) are limited by blood-brain barrier penetration and T790M tumor mutations, wherein third-generation EGFR-TKIs, like Osimertinib, have shown greater activity. However, their efficacy has not been well-studied in later therapy lines in NSCLC patients with BMs (NSCLC-BM). We sought to compare outcomes of NSCLC-BM treated with either first- or third-generation EGFR-TKIs in first-line and 2nd-to-5th-line settings. Methods: A retrospective review of NSCLC-BM patients diagnosed during 2010–2019 at Cleveland Clinic, Ohio, US, a quaternary-care center, was performed and reported following ‘strengthening the reporting of observational studies in epidemiology’ (STROBE) guidelines. Data regarding socio-demographic, histopathological, molecular characteristics, and clinical outcomes were collected. Primary outcomes were median overall survival (mOS) and progression-free survival (mPFS). Multivariable Cox proportional hazards modeling and propensity score matching were utilized to adjust for confounders. Results: 239 NSCLC-BM patients with EGFR alterations were identified, of which 107 received EGFR-TKIs after diagnosis of BMs. 77.6% (83/107) received it as first-line treatment, and 30.8% (33/107) received it in later (2nd–5th) lines of therapy, with nine patients receiving it in both settings. 64 of 107 patients received first-generation (erlotinib/gefitinib) TKIs, with 53 receiving them in the first line setting and 13 receiving it in the 2nd–5th lines of therapy. 50 patients received Osimertinib as third-generation EGFR-TKI, 30 in first-line, and 20 in the 2nd–5th lines of therapy. Univariable analysis in first-line therapy demonstrated mOS of first- and third-generation EGFR-TKIs as 18.2 and 19.4 months, respectively (p = 0.57), while unadjusted mPFS of first- and third-generation EGFR-TKIs was 9.3 and 13.8 months, respectively (p = 0.14). In 2nd–5th line therapy, for first- and third-generation EGFR-TKIs, mOS was 17.3 and 11.9 months, (p = 0.19), while mPFS was 10.4 and 6.08 months, respectively (p = 0.41). After adjusting for age, performance status, presence of extracranial metastases, whole-brain radiotherapy, and presence of leptomeningeal metastases, hazard ratio (HR) for OS was 1.25 (95% CI 0.63–2.49, p = 0.52) for first-line therapy. Adjusted HR for mOS in 2nd-to-5th line therapy was 1.60 (95% CI 0.55–4.69, p = 0.39). Conclusions: No difference in survival was detected between first- and third-generation EGFR-TKIs in either first or 2nd-to-5th lines of therapy. Larger prospective studies are warranted reporting intracranial lesion size, EGFR alteration and expression levels in primary tumor and brain metastases, and response rates.

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Section: Discussionmentioning

confidence: 99%

First- versus Third-Generation EGFR Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases

Tatineni

O’Shea

Ozair

et al. 2023

Cancers

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“…In our study, patients with liver metastasis showed significantly shorter PFS and OS, consistent with those previous findings. A very recent real-world study comparing the efficacies of different EGFR-TKIs showed that osimertinib, a third-generation EGFR -TKI, was not superior over other TKIs in patients with liver metastasis, while it provided significant clinical benefits in patients with brain or bone metastasis [ 35 ]. The association between liver metastasis and poor prognosis has been consistently reported across different treatment settings, including immunotherapy [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

High Tumor Mutation Burden Is Associated with Poor Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy

2022

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This study aimed to determine the association between TMB and treatment outcomes in patients with epidermal growth factor receptor (EGFR)-mutated lung cancer that were treated with tyrosine kinase inhibitors (TKIs). The TMB was assessed using a 409-gene targeted next-generation sequencing panel. We compared the response rate (RR), progression-free survival (PFS), overall survival (OS), and frequency of secondary T790M mutations among the different TMB groups. The median TMB of the study population (n = 88) was 3.36/megabases. We divided 52 (59%) and 36 (41%) patients into the low and high TMB groups, respectively. A high TMB level was significantly associated with liver metastasis and more advanced stage (all p < 0.05). RR was significantly lower in the high TMB group than that of the low TMB group (50.0% vs. 80.7%, all p = 0.0384). In multivariate analysis, high TMB was independently associated with a shorter PFS (hazard ratio [HR] = 1.80, p = 0.0427) and shorter OS (HR = 2.05, p = 0.0397) than that of the low TMB group. Further, high TMB was independently associated with decreased T790M mutation development. These results suggest that high TMB may be a predictive biomarker for adverse treatment outcomes and represent a patients’ subgroup warranting tailored therapeutic approaches.

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“…3 Lung cancer patients who harbor LM often have significantly shorter progression-free survival (PFS) and overall survival (OS) compared to those with distant metastases in other organs. 3,4 The epidermal growth factor receptor (EGFR) mutation is the most common targetable driver mutation in lung cancer. 5 In the past decade, EGFR-tyrosine kinase inhibitors (TKIs) were suggested as the first-line therapy for patients with EGFR mutant lung cancer.…”

Section: Introductionmentioning

confidence: 99%

“…5 In the past decade, EGFR-tyrosine kinase inhibitors (TKIs) were suggested as the first-line therapy for patients with EGFR mutant lung cancer. 4 In current clinical practice, the tissue biopsy is routinely used to evaluate the EGFR mutation status. 6 And the distant metastasis is an important alternative if the primary tumor is unavailable to be sampled.…”

Section: Introductionmentioning

confidence: 99%

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Tumor‐liver interface in MRI of liver metastasis enables prediction of EGFR mutation in patients with lung cancer: A proof‐of‐concept study

Hou,

Wang,

Wang

et al. 2023

Medical Physics

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BackgroundPreoperative prediction of the epidermal growth factor receptor (EGFR) status in non‐small‐cell lung cancer (NSCLC) patients with liver metastasis (LM) may have potential clinical values for assisting in treatment decision‐making.PurposeTo explore the value of tumor‐liver interface (TLI)‐based magnetic resonance imaging (MRI) radiomics for detecting the EGFR mutation in NSCLC patients with LM.MethodsThis retrospective study included 123 and 44 patients from hospital 1 (between Feb. 2018 and Dec. 2021) and hospital 2 (between Nov. 2015 and Aug. 2022), respectively. The patients received contrast‐enhanced T1‐weighted (CET1) and T2‐weighted (T2W) liver MRI scans before treatment. Radiomics features were extracted from MRI images of TLI and the whole tumor region, separately. The least absolute shrinkage and selection operator (LASSO) regression was used to screen the features and establish radiomics signatures (RSs) based on TLI (RS‐TLI) and the whole tumor (RS‐W). The RSs were evaluated by the receiver operating characteristic (ROC) curve analysis.ResultsA total of 5 and 6 features were identified highly correlated with the EGFR mutation status from TLI and the whole tumor, respectively. The RS‐TLI showed better prediction performance than RS‐W in the training (AUCs, RS‐TLI vs. RS‐W, 0.842 vs. 0.797), internal validation (AUCs, RS‐TLI vs. RS‐W, 0.771 vs. 0.676) and external validation (AUCs, RS‐TLI vs. RS‐W, 0.733 vs. 0.679) cohort.ConclusionOur study demonstrated that TLI‐based radiomics can improve prediction performance of the EGFR mutation in lung cancer patients with LM. The established multi‐parametric MRI radiomics models may be used as new markers that can potentially assist in personalized treatment planning.

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Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

Cited by 25 publications

References 37 publications

First- versus Third-Generation EGFR Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases

First- versus Third-Generation EGFR Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases

High Tumor Mutation Burden Is Associated with Poor Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy

Tumor‐liver interface in MRI of liver metastasis enables prediction of EGFR mutation in patients with lung cancer: A proof‐of‐concept study

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