Upfront management of brain metastases in oncogene‑addicted NSCLC – An EORTC survey

BACKGROUND: Brain metastases (BM) are common in patients with non-small cell lung cancer (NSCLC) harboring actionable genomic alterations (AGA). The availability of next-generation targeted therapies (TT) with improved central nervous system activity has expanded systemic treatment options. However, the optimal upfront management of untreated symptomatic and asymptomatic BM remains uncertain due to limited trial data. METHODS: A web-based survey was conducted by the EORTC Lung Cancer Group and distributed to EORTC and ESTRO members in June 2023-July 2024. The survey evaluated diagnostic approaches, access to TT and upfront management of untreated BM across 10 different AGA (including EGFR, ALK, ROS1, and others). Responses were analysed descriptively and stratified by neurological symptom status, AGA, intracranial objective response rate (icORR) of available TT, and medical specialty. RESULTS: A total of 166 responses were analysed (91.0% of respondents worked in Europe, 47.6% were medical oncologist, 36.1% radiation oncologist, 9.6% pneumonologist, 4.8% clinical oncologist). For asymptomatic BM, 68.8% of physicians preferred upfront TT across AGA. In symptomatic BM, preferred upfront treatment included: local therapy alone (43.0%), TT alone (19.0%), local therapy or TT depending on other factors (35.4%). Treatment preferences for (a)symptomatic BM varied according to AGA, icORR of available TT, and medical specialty. In cases of brain oligoprogression, addition of local treatment and TT beyond progression was the most common option (92% of respondents). Across AGA, 35-52% of respondents opted to discontinue TT during brain radiotherapy with no clear preference for TT discontinuation timing. CONCLUSIONS: This work provides insights on the preferred upfront management of BM in patients with NSCLC and AGAs and underscores some of the challenges in this area, including extrapolation of data and uncertainty about how best to integrate TT with local therapies. Our findings might help identify priorities for future research and guideline development.