MA 09.05 Evidence in Favor of or against the Use of TKIs with Concurrent Cranial Radiotherapy in Patients with NSCLC and CNS Involvement

Abstract

Central nervous system (CNS) metastases, including brain metastases (BM) and leptomeningeal metastases (LM) represent a frequent complication of non-small cell lung cancer (NSCLC). Patients with CNS metastases comprise a heterogeneous group, with a median survival that ranges from 3 to 14 months. Local therapies, such as whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) or surgical resection, are available treatment strategies for BM. Introduction of tyrosine kinase inhibitors (TKIs) in clinical practice has led to individualization of therapy based upon the presence of the exact abnormality, resulting in a major therapeutic improvement in patients with NSCLC who harbor epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK) gene rearrangements, respectively, but their role in combination with radiotherapy is controversial. We performed a systematic literature review of published data in PUBMED, SCOPUS and COCHRANE databases, as well as a manual search of reported data in major congresses, using the terms “EGFR-TKIs”, “ALK-TKIs”, “CNS”, “BM” or ““LM” and “concurrent radiotherapy” or “stereotactic radiotherapy” from January 2000 through May 2017. Only prospective or retrospective clinical trials and meta-analyses reported in English language were included. See Table. At this time, concurrent use of TKIs with radiotherapy, although appearing to be safe, is not recommended outside of a clinical trial. Interestingly, data in EGFR mutant patients treated with an EGFR-TKI alone prompt the question whether this could be a front line approach in patients with asymptomatic BM, reserving WBRT for symptomatic cases. In clinical practice, burden of extracranial disease might also guide treatment decisions; physicians might select not to discontinue a TKI during WBRT in case of extensive extracranial organ involvement Ongoing clinical trials are currently evaluating the effectiveness of concomitant use of radiotherapy and TKIs.