Role of Epidermal Growth Factor Receptor (EGFR) Inhibitors and Radiation in the Management of Brain Metastases from EGFR Mutant Lung Cancers

Khandekar, Melin J.; Piotrowska, Zofia; Willers, Henning; Sequist, Lecia V.

doi:10.1634/theoncologist.2017-0557

Cited by 10 publications

(11 citation statements)

References 58 publications

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“…Alectinib could induce a meaningful response in these patients while allowing prompt initiation of systemic therapy and postponement (or elimination) of the need for brain radiation, with potential sparing from the associated short-and longterm neurotoxicities. [11][12][13][14] For these patients, careful multidisciplinary evaluation at the initial presentation involving the surgical, radiation oncology, and medical oncology teams will be critical, with close clinical followup upon the start of alectinib therapy and early assessment of radiologic response if warranted. Of note, this study did not compare outcomes in patients treated with alectinib first with those in patients treated with CNS RT followed by alectinib.…”

Section: Discussionmentioning

confidence: 99%

“…The 1-cm cutoff was selected because clinicians may use it as a threshold to determine whether to proceed with CNS RT. 12 Prior CNS RT was allowed if the aforementioned criteria were met, with unequivocal tumor growth of the metastatic lesion after radiation. Data on clinicopathologic features were extracted under an institutional review board-approved protocol.…”

Section: Patients and Data Collectionmentioning

confidence: 99%

“…At present, the standard therapy for symptomatic or large brain lesions remains surgical resection, stereotactic radiosurgery (SRS), whole brain radiotherapy (RT), or some combination thereof, which may delay the initiation of systemic therapy and cause short-and long-term neurotoxicities, including radionecrosis and cognitive impairment. [11][12][13][14] Herein, we report the CNS efficacy of alectinib in ALK-positive NSCLC, focusing on patients with baseline CNS metastases that were symptomatic or at least 1 cm in size.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Lin

Jiang

Joshipura

et al. 2019

Journal of Thoracic Oncology

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Background: Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases. Methods: In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as 1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval [CI]: 44.9%-92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%-100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months-not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%-90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%-100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months-not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy. Conclusions: Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases.

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Section: Discussionmentioning

confidence: 99%

Section: Patients and Data Collectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Lin

Jiang

Joshipura

et al. 2019

Journal of Thoracic Oncology

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“…With the recent progress in novel EGFR-TKIs, a fervent debate on the omission or delay of brain RT for EGFR-mutated NSCLC BMs by using TKIs alone has been rekindled (29–31). To our knowledge, this is the largest meta-analysis that evaluated the efficacy of upfront RT vs. EGFR-TKI alone in management of TKI-naïve EGFR-mutated NSCLC BMs by using all comparative studies.…”

Section: Discussionmentioning

confidence: 99%

Upfront Cranial Radiotherapy vs. EGFR Tyrosine Kinase Inhibitors Alone for the Treatment of Brain Metastases From Non-small-cell Lung Cancer: A Meta-Analysis of 1465 Patients

Pan

Lai

et al. 2018

Front. Oncol.

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Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is revolutionizing the management of brain metastases (BMs). This study was to explore the value of upfront cranial radiotherapy (RT) in EGFR-mutated non-small cell lung cancer (NSCLC) with BMs compared with EGFR-TKIs alone.Methods: We searched all topic-related comparative articles in public databases (MEDLINE, EMBASE, Cochrane Library, and Web of Science) and conference proceedings. Outcomes of interest were intracranial objective response rate (ORR), overall survival (OS), and intracranial progression-free survival (PFS). Statistical analyses were calculated using Review Manager 5.3 software.Results: Thirteen comparative studies that included a total of 1,456 patients were eligible. Upfront brain RT had significantly higher OS (HR = 0.78, 95% CI = 0.65–0.93, P = 0.005) than EGFR-TKI alone. Upfront RT plus TKI had superior OS (HR = 0.71, 95% CI = 0.58–0.86, P = 0.0005) and intracranial PFS (HR = 0.69, 95% CI = 0.49–0.99, P = 0.04). The pooled data favored upfront whole brain RT (WBRT) plus TKI in terms of intracranial PFS (HR = 0.64, 95% CI = 0.48–0.85, P = 0.002) and OS (HR = 0.75, 95% CI = 0.57–1, P = 0.05). Upfront stereotactic radiosurgery (SRS) was associated with better OS (HR = 0.37, 95% CI = 0.26–0.54, P < 0.00001). Similar results were observed when analysis was restricted to the use of erlotinib or geftinib.Conclusions: The upfront use of brain RT seemed critical, especially for SRS. Upfront administration of upfront WBRT plus EGFR-TKI had better survival outcomes and seemed superior to EGFR-TKI alone.

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“…These mutations can be seen in current smokers, ex-smokers and non-smokers, whereas mutations in EGFR, ALK, HER2, ROS1 and RET genes are seen only in people who have never smoked. Such mutations may be observed in all histological subgroups of NSCLCs including adenocarcinomas, squamous cell carcinomas (SCCs) and large cell carcinomas [7][8][9][10].…”

Section: Mutations In Lung Cancermentioning

confidence: 99%

Epigenetic Modifications and Potential Treatment Approaches in Lung Cancers

Budak¹,

Yıldız²

2018

Lung Cancer - Strategies for Diagnosis and Treatment

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Alteration of methylation is a process seen across a wide variety of species ranging from bacterial microorganisms to mammals, defined as the adaptation method the organism develops against environmental or intrinsic effects, or employs to switch off the genome regions which are no longer required through the evolutionary process. Scientific advancements have allowed detecting the regions that undergo different patterns of methylation. It has been demonstrated that the control on changes in gene expression is not guided by transcription factors alone and that epigenetic alterations are also involved in this process. Furthermore, epigenetic modifications have been shown to be considerably important in cancer development. This section focuses on epigenetic changes and potential treatment options in lung cancer.

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Role of Epidermal Growth Factor Receptor (EGFR) Inhibitors and Radiation in the Management of Brain Metastases from EGFR Mutant Lung Cancers

Cited by 10 publications

References 58 publications

Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Upfront Cranial Radiotherapy vs. EGFR Tyrosine Kinase Inhibitors Alone for the Treatment of Brain Metastases From Non-small-cell Lung Cancer: A Meta-Analysis of 1465 Patients

Epigenetic Modifications and Potential Treatment Approaches in Lung Cancers

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