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. 2020 Sep 3:2020:1980891.
doi: 10.1155/2020/1980891. eCollection 2020.

Tyrosine Kinase Inhibitors as a Treatment of Symptomatic CNS Metastases in Oncogene-Driven NSCLC

Omer Gal #  1   2 , Elizabeth Dudnik #  2   3 , Ofer Rotem  2   3 , Inbar Finkel  2   3 , Idit Peretz  2   3 , Alona Zer  2   3 , Jacob Mandel  4 , Alexandra Amiel  1   2 , Tali Siegal  1 , Jair Bar  2   5 , Anastasiya Lobachov  2   5 , Shlomit Yust  1   2
Affiliations

Tyrosine Kinase Inhibitors as a Treatment of Symptomatic CNS Metastases in Oncogene-Driven NSCLC

Omer Gal et al. J Oncol. .

Abstract

Central nervous system (CNS) metastases occur frequently in oncogene-driven non-small cell lung cancer (NSCLC). Standard treatment approaches can potentially delay systemic treatment (surgical intervention) or result in neurocognitive impairment (radiotherapy). Recently, next-generation tyrosine kinase inhibitors (TKIs) have demonstrated remarkable intracranial activity. However, most clinical trials did not enroll patients suffering neurological symptoms. Our study aimed to assess the CNS activity of targeted therapies in this patient population. We present a case series of nine NSCLC patients with either EGFR mutation or ALK rearrangement and symptomatic CNS metastases that were treated with TKIs. Clinicopathological characteristics, treatment, and outcomes were analyzed. Most patients presented with symptomatic CNS metastases at time of metastatic disease presentation (6/9). Additionally, the majority of patients had leptomeningeal disease (6/9) and multiple parenchymal metastases. Patients presented with a variety of CNS symptoms with the most common being nausea, vomiting, headache, and confusion. Most patients (6/9) responded rapidly both clinically and radiographically to the targeted treatment, with a marked correlation between systemic and intracranial radiographic response. In conclusion, upfront use of next-generation TKIs in patients with oncogene-driven NSCLC with symptomatic CNS metastases is associated with reasonable intracranial activity and represents a valuable treatment option.

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Conflict of interest statement

Elizabeth Dudnik reported grants from Boehringer Ingelheim and personal fees for consulting or advisory services from Boehringer Ingelheim, Roche, Astra Zeneca, Pfizer, MSD, BMS, Novartis, and Takeda. Alona Zer reported grants from BMS and personal fees for consulting or advisory services from Roche, MSD, BMS, and AstraZeneca. Jacob Mandel served on a medical advisory board for Bayer. Jair Bar reported grants from MSD, Roche, AstraZeneca, and Pfizer and reported personal fees for consulting or advisory services from MSD, Roche, Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, Takeda, VBL, Bayer, Novartis, and AbbVie. Shlomit Yust reported grants from MSD and and personal fees from AbbVie. Other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Dynamics of brain metastases on lorlatinib. Axial brain CT showing brain metastases (white arrows) after lorlatinib dose reduction (a). Axial brain MRI (T1 with contrast) performed two months after resuming full dose lorlatinib showing complete resolution of all brain lesions (b).
Figure 2
Figure 2
Dynamics of brain metastases on osimertinib. Brain MRI (T1 with contrast, axial, and sagittal) showing brain metastases (white arrows) before treatment (a and c) and 1 month after initiating treatment (b and d).
See this image and copyright information in PMC

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