Targeted therapy is the preferred initial approach for asymptomatic brain metastases in oncogene-addicted non-small cell lung cancer (NSCLC), according to a recent survey, although uncertainty remains about the management of symptomatic disease and the use of radiotherapy with targeted agents.

Brain metastases are a common complication of NSCLC harbouring actionable genomic alterations, particularly epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 alterations.

The development of next-generation tyrosine kinase inhibitors with improved central nervous system (CNS) activity has broadened treatment options and raised questions about whether local therapies, such as surgery and radiotherapy, can be deferred in selected patients.

To explore current practice patterns, investigators from the European Organisation for Research and Treatment of Cancer (EORTC) Lung Cancer Group conducted a web-based survey among members of EORTC and the European Society for Radiotherapy and Oncology.

Published in the journal Lung Cancer, the survey assessed diagnostic approaches, access to targeted therapies and preferences for the upfront management of untreated brain metastases across 10 actionable molecular subtypes of NSCLC.

Brain metastases and NSCLC treatment decisions

The survey included responses from 166 clinicians, 91% of whom were based in Europe. Medical oncologists accounted for 47.6% of respondents and radiation oncologists for 36.1%, with the remainder comprising pneumonologists, clinical oncologists and molecular biologists. Most worked in academic centres and had more than 10 years of clinical experience.

The survey’s primary focus was the preferred upfront management of untreated brain metastases in patients with oncogene-addicted NSCLC. Secondary areas included screening practices, management of brain oligoprogression and approaches to combining targeted therapy with radiotherapy.

Across 1,287 evaluable responses, targeted therapy was the preferred initial treatment for asymptomatic brain metastases, selected in 68.8% of cases. In contrast, symptomatic brain metastases prompted a preference for local treatment, with 43.0% choosing surgery and/or radiotherapy.

A further 35.4% favoured either local therapy or targeted treatment depending on clinical factors, while only 19.0% selected upfront targeted therapy alone.

Treatment preferences varied according to molecular subtype, intracranial objective response rates of available therapies and clinician speciality. Upfront targeted therapy was particularly favoured for EGFR-, ALK- and ROS1-driven disease, where CNS-active agents have demonstrated high intracranial efficacy.

Lack of consensus on radiotherapy integration

The survey identified broad agreement on the management of brain oligoprogression, with more than 92% of respondents favouring continuation of targeted therapy beyond progression, alongside local treatment for intracranial disease control.

However, considerable variation emerged regarding the use of radiotherapy with targeted agents.

Depending on molecular subtype, 35–52% of respondents reported discontinuing targeted treatment during brain radiotherapy, whereas 40–55% continued therapy throughout treatment. No clear consensus was identified regarding the timing of treatment interruption.

Key factors influencing treatment decisions included the targeted agent’s CNS penetration, intracranial and extracranial disease burden, patient fitness, and lesion location. Fewer than 40% of respondents reported routinely considering patient preference.

Although almost all clinicians had access to multidisciplinary tumour boards, only around half discussed all patients with brain metastases and actionable alterations in a multidisciplinary setting.

The authors acknowledged several study limitations. The survey was descriptive, involved a relatively small sample and largely reflected practice in European academic centres, which may limit generalisability.

Response rates were unknown, the intracranial response rate classification used was not validated, and the questionnaire did not capture factors such as the number or location of brain metastases. In addition, newer CNS-active therapies that became available after the survey was developed were not assessed.

The authors concluded that the management of brain metastases in oncogene-addicted NSCLC remains a considerable clinical uncertainty.

The need for prospective registries, pragmatic clinical trials and stronger multidisciplinary collaboration to inform future consensus guidelines, particularly for patients with symptomatic brain metastases who are often excluded from randomised studies, was also highlighted.

Reference
Ortega-Franco A et al. Upfront management of brain metastases in oncogene-addicted NSCLC – An EORTC survey. Lung Cancer 2026;217:109444.