Dataset Information

Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis.

ABSTRACT:

Background

The impact of activating alterations in non-small cell lung cancer (NSCLC) (epidermal growth factor receptor [EGFR] mutation/anaplastic lymphoma kinase [ALK] translocation) in prognosticating patients with brain metastasis (BM) is not well defined. This study was sought to identify this impact in NSCLC patients with BM accounting for the known validated variables.

Methods

Among 1078 NSCLC-BM patients diagnosed/treated between January 1, 2000 and December 31, 2015, three hundred and forty-eight with known EGFR/ALK status were analyzed. Overall survival (OS) and intracranial progression-free survival (PFS) were measured from the time of BM.

Results

Ninety-one patients had either ALK (n = 23) alterations or EGFR (n = 68) mutation and 257 were wild type (WT; negative actionable mutations/alterations). Median age of EGFR/ALK+ NSCLC BM patients was 60 years (range 29.8-82.6 y) and ~50% (n = 44) had Karnofsky performance status (KPS) score >80. Median number of BM was 2 (1 to ?99). The median OS for the ALK/EGFR+ NSCLC BM was 19.9 versus 10.1 months for the WT (P = 0.028). The number of BM in the EGFR/ALK+ group did not impact OS (BM = 1 with 21.1 months vs 2-3 with 19.1 months and >3 with 23.7 months, P = 0.74), whereas fewer BM in the WT cohort had significantly better OS (BM = 1 with 13.8 mo, 2-3 with 11.0 mo and >3 with 8.1 mo; P = 0.006) with the adjustment of age, KPS, symptoms from BM and synchronicity.

Conclusions

Number of BM does not impact outcomes in the EGFR/ALK+ NSCLC patients, implying that targeted therapy along with surgery and/or radiation may improve OS irrespective of the number of BM. Number of BM, extracranial metastasis (ECM), and KPS independently affected OS/PFS in WT NSCLC BM, which was consistent with the known literature.

SUBMITTER: Balasubramanian SK

PROVIDER: S-EPMC7442419 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis.

Balasubramanian Suresh K SK Sharma Mayur M Venur Vyshak A VA Schmitt Philipp P Kotecha Rupesh R Chao Samuel T ST Suh John H JH Angelov Lilyana L Mohammadi Alireza M AM Vogelbaum Michael A MA Barnett Gene H GH Jia Xuefei X Pennell Nathan A NA Ahluwalia Manmeet S MS

Neuro-oncology 20200201 2

<h4>Background</h4>The impact of activating alterations in non-small cell lung cancer (NSCLC) (epidermal growth factor receptor [EGFR] mutation/anaplastic lymphoma kinase [ALK] translocation) in prognosticating patients with brain metastasis (BM) is not well defined. This study was sought to identify this impact in NSCLC patients with BM accounting for the known validated variables.<h4>Methods</h4>Among 1078 NSCLC-BM patients diagnosed/treated between January 1, 2000 and December 31, 2015, three ...[more]

PMID: 31648302

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Project description:IntroductionRadiotherapy (RT) is currently the main treatment for brain metastases (BMs) from non-small cell lung cancer (NSCLC). Due to the short survival time and obvious adverse reactions of RT, we urgently need more appropriate treatment. This network meta-analysis reviewed the efficacy and adverse effects of radiotherapy-based combination therapy for patients without targeted epidermal growth factor receptor (EGFR) mutations/anaplastic lymphoma kinase (ALK) gene rearrangement NSCLC BMs, to screen out the therapy with the best efficacy.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from the earliest publication date available to 1 April 2022. STATA15.0 was used to conduct heterogeneity analysis, sensitivity analysis, forest plot analysis, and publication bias analysis.ResultsA total of 28 studies, involving 3707 patients were included in the Bayesian network meta-analysis. In the limited paired meta-analysis for head-to-head comparative trials, compared with RT-based combination therapy, RT combined with Immune checkpoint inhibitors (ICIs) showed significant overall survival (OS) benefit (HR 0.65, 95%CI 0.47-0.9, p<0.01), RT combined with ICIs showed a non-significant difference for intracranial progression-free survival (iPFS) (HR 0.76, 95%CI 0.27-2.27, p<0.01) and progression-free survival (PFS) (HR 0.9, 95%CI 0.36-2.37, p<0.01). In addition, according to the ranking results, compared with RT combined with chemotherapy(CT) or with targeted therapy(TT), RT combined with ICIs might be the best treatment mode for OS(ICIs+RT vs CT+RT vs TT+RT; 91.9% vs. 27.8% vs. 29.3%, iPFS (ICIs+RT vs CT+RT vs TT+RT, 46.9% vs 25.2% vs 25.6%) and PFS (ICIs+RT vs CT+RT vs TT+RT, 36.2% vs 31% vs 36.5%).ConclusionsRT combined with ICIs might be the best treatment mode to prolong the OS for BMs from NSCLC with non-EGFR mutation/ALK gene rearrangement.Review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022350065, identifier (CRD42022350065).

Project description:BackgroundBrain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements.MethodsWe searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS).ResultsWe included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24).ConclusionsIn patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060.

Project description:The present study aimed to investigate the association between epidermal growth factor receptor (EGFR)/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and the morphological characteristics of lung adenocarcinoma (LAC), according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification in a large group of patients with primary LAC. A total of 200 patients with invasive LAC who had undergone complete resections at the Beijing Chest Hospital (Beijing, China) were randomly selected. The morphology of the samples was reassessed in 5% increments by two pathologists, according to the IASLC/ATS/ERS scheme. EGFR and KRAS mutations were tested by direct DNA sequencing. ALK rearrangements were screened by immunohistochemistry on a Benchmark XT stainer. The data revealed that EGFR and KRAS mutations, and ALK rearrangements were identified in 46.0% (92/200), 9.0% (18/200) and 11.5% (23/200) of the patients, respectively. The EGFR/KRAS mutations and ALK rearrangements were mostly exclusive. However, 1 patient exhibited the coexistence of the EGFR (at exon 20) and KRAS (codon 12) mutations, and another patient exhibited the coexistence of the EGFR mutation (at exon 21) and the ALK gene fusion. EGFR mutations were indicated to be closely associated with the acinar predominant (43/77; 55.8%; P=0.030) and papillary predominant (26/49; 53.1%; P=0.006) subtypes. KRAS mutations were more commonly associated with the solid predominant subtype (9/52; 17.3%; P=0.023) and invasive mucinous LAC (5/10; 50.0%; P=0.004), and less commonly associated with the acinar predominant subtype (1/77; 1.3%; P=0.002). ALK rearrangements more commonly occurred in the solid predominant subtype compared with other subtypes (13/52; 25%; P=0.002), and less commonly occurred in the papillary predominant subtype (1/49; 2.0%; P=0.004). Tumors harboring ALK rearrangements were characterized by signet-ring cell (7/9; 77.8%; P<0.0001) and cribriform (7/12; 58.3%; P<0.0001) patterns. The association between the mutation status and histological subtype in LAC was distinct. The predominant subtype according to the IASLC/ATS/ERS classification provided important information for gene mutations and integrated clinical findings to improve the treatment of LAC patients.

Dataset Information

Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis.

Background

Methods

Results

Conclusions

Publications

Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis.

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