Dataset Information

The Efficacy of Upfront Intracranial Radiation with TKI Compared to TKI Alone in the NSCLC Patients Harboring EGFR Mutation and Brain Metastases.

ABSTRACT: Introduction: The high intracranial efficacy of EGFR-TKI challenges the role of upfront intracranial radiation therapy (RT) in non-small cell lung cancer (NSCLC) patients with EGFR mutation and brain metastases (BM). Therefore, we conducted a retrospective analysis to demonstrate the role of upfront RT in these patients. Materials and Methods: Patients that had histologically confirmed NSCLC with EGFR mutation, brain metastases, and received TKI or upfront RT with TKI were included in this study. Intracranial progression was estimated using the Fine-Gray competing risks model. Kaplan-Meier analysis and Log-rank test were used to evaluate and compare intracranial progression-free survival (iPFS), systemic PFS (sPFS), time to second-line systematic therapy (SST) and overall survival (OS). Results: Among the 93 patients included, 53 patients received upfront RT and TKI, and 40 patients received TKI only. Upfront RT group showed lower intracranial progression risk with adjusted SHR 0.38 (95% CI, 0.19 to 0.75, P= 0.006) and longer median time to sPFS (15.6 vs 8.9 months, P= 0.009). There were 9 out of 36 (25%) and 16 out of 34 (47.1%) patients who had oligo-progression received salvage RT in the RT group and TKI group, respectively. After the salvage RT, upfront RT did not prolong the median time to SST (23.6 vs 18.9 months, P=0.862) and OS (median time, 35.4 vs 35.8 months, P=0.695) compared to TKI alone. Conclusion: Compared to upfront intracranial RT, the salvage RT to oligo-progressive disease allowed patients getting TKI to have similar time on initial TKI and OS despite worse iPFS. The best timing of intracranial RT remains to be further verified.

SUBMITTER: Wang C

PROVIDER: S-EPMC6548172 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Efficacy of Upfront Intracranial Radiation with TKI Compared to TKI Alone in the NSCLC Patients Harboring EGFR Mutation and Brain Metastases.

Wang Chunyu C Lu Xiaotong X Zhou Zongmei Z Wang Jingbo J Hui Zhouguang Z Liang Jun J Feng QinFu Q Chen Dongfu D Xiao Zefen Z Lv Jima J Wang Xiaozhen X Wang Xin X Zhang Tao T Deng Lei L Wang Wenqing W Xiao Jianping J Li Junling J Bi Nan N Wang Luhua L

Journal of Cancer 20190512 9

<b>Introduction:</b> The high intracranial efficacy of EGFR-TKI challenges the role of upfront intracranial radiation therapy (RT) in non-small cell lung cancer (NSCLC) patients with EGFR mutation and brain metastases (BM). Therefore, we conducted a retrospective analysis to demonstrate the role of upfront RT in these patients. <b>Materials and Methods:</b> Patients that had histologically confirmed NSCLC with EGFR mutation, brain metastases, and received TKI or upfront RT with TKI were included ...[more]

PMID: 31205558

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Project description:PurposeWe aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)-mutated patients with or without concomitant alterations.Materials and methodsThis multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non-small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR-tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.ResultsThe overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.ConclusionEGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

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Dataset Information

The Efficacy of Upfront Intracranial Radiation with TKI Compared to TKI Alone in the NSCLC Patients Harboring EGFR Mutation and Brain Metastases.

Publications

The Efficacy of Upfront Intracranial Radiation with TKI Compared to TKI Alone in the NSCLC Patients Harboring EGFR Mutation and Brain Metastases.

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